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Showing papers on "Adenocarcinoma of the lung published in 1995"


Journal ArticleDOI
15 Jun 1995-Cancer
TL;DR: The clinicopathologic characteristics and prognostic factors of early stage adenocarcinoma have not been evaluated fully, except for several studies of nonmucinous and sclerosing bronchioloalveolar carcinoma.
Abstract: Background. Although there are many reported prognostic indicators for pulmonary adenocarcinoma, the clinicopathologic characteristics and prognostic factors of early stage adenocarcinoma have not been evaluated fully, except for several studies of nonmucinous and sclerosing bronchioloalveolar carcinoma. Method. Two hundred thirty-six surgically resected small peripheral adenocarcinomas measuring 2 cm or less in greatest dimension were reviewed using a simple histologic classification of six types based on tumor growth patterns. Results. Type A (localized bronchioloalveolar carcinoma [LBAC]) (n = 14) revealed replacement growth of alveolar-lining epithelial cells with a relatively thin stroma. In type B (LBAC with foci of structural collapse of alveoli) (n = 14), fibrotic foci due to alveolar collapse were observed in tumors of LBAC. Type C (LBAC with foci of active fibroblastic proliferation) (n = 141) was the largest group in this study, and foci of active fibroblastic proliferation were evident. Type D (poorly differentiated adenocarcinoma), type E (tubular adenocarcinoma) and type F (papillary adenocarcinoma with a compressive growth pattern) (n = 61) showed compressive and expanding growth. Types A and B showed no lymph node metastasis and the most favorable prognosis (100% 5-year survival) of the six types. Conclusion. Histologic types A and B are thought to be in situ peripheral adenocarcinoma, whereas type C appears to be an advanced stage of types A and B. Conversely, types D, E, and F are small advanced adenocarcinomas with a less favorable prognosis. Cancer 1995;75:2844–52.

1,176 citations


Journal ArticleDOI
TL;DR: The subset of non-small-cell lung cancers that exhibits only low or undetectable levels of telomerase activity may contain primarily mortal cancer cells, which are likely to consist mainly of immortal cells.
Abstract: Background : Telomerase is an enzyme that adds hexameric TTAGGG nucleotide repeats onto the ends of vertebrate chromosomal DNAs (i.e., telomeres) to compensate for losses that occur with each round of DNA replication. Somatic cells do not have telomerase activity and stop dividing when the telomeric ends of at least some chromosomes have been shortened to a critical length. It has been suggested that immortalized cells (including some, but probably not all, cancer cells) continue to proliferate indefinitely because they express telomerase. Purpose : To investigate whether expression of telomerase is a prerequisite for the development of naturally occurring human cancers, we assayed the levels of telomerase activity in specimens of human lung tumor and adjacent normal tissue. Methods : Using a polymerase chain reaction-based assay, we examined telomerase activity in 136 primary lung cancer tissues and 68 adjacent noncancerous tissues obtained by surgical resection. We also studied telomerase activity in four primary and 23 metastatic lesions obtained through biopsy (two patients) or autopsy (10 patients). Relative telomerase activity levels were estimated by serial dilutions of extracts prepared from the specimens. Telomerase activity was also assayed in extracts of cells present in pleural fluids from three patients with adenocarcinoma of the lung. Results : Among surgically resected samples, telomerase activity was detected in 109 (80.1%) of 136 primary lung cancer tissues and in three (4.4%) of 68 normal adjacent tissues. All 11 surgically resected specimens of primary small-cell lung cancer (from 11 patients) revealed high levels of telomerase activity, whereas the activity ranged from undetectable to high levels in the 125 surgically resected specimens of primary non-small-cell lung cancer tissue (from 125 patients). Generally, high levels of telomerase activity were observed in metastatic lesions and tumors with altered telomere length. A few primary and, surprisingly, some metastatic tumors did not appear to have detectable telomerase activity. Telomerase activity was, however, detected in cells present in all tested pleural fluids obtained (from three patients with adenocarcinoma of the lung). Conclusion : The subset of non-small-cell lung cancers that exhibits only low or undetectable levels of telomerase activity may contain primarily mortal cancer cells. Cancers that exhibit high levels of telomerase activity, such as all of the small-cell lung cancers examined in this study, are likely to consist mainly of immortal cells. Implications: Telomerase activity may be useful both as a diagnostic marker to detect the existence of immortal lung cancer cells in clinical materials and as a target for therapeutic intervention. [J Natl Cancer Inst 87 :895-902, 1995]

460 citations


Journal ArticleDOI
TL;DR: The steeper increase during recent decades of lung adenocarcinoma incidence compared with squamous cell carcinoma of the lung is discussed, as well as the likely underlying factors for increased lung cancer risk among African Americans compared with that among white Americans.
Abstract: In 1950, the first large-scale epidemiological studies demonstrated that lung cancer is causatively associated with cigarette smoking, a finding subsequently confirmed by the Royal College of Physicians in London, the U.S. Surgeon General, and the World Health Organization. Although cigarette consumption has gradually decreased in the United States from a high of about 3800 cigarettes per adult per year in 1965 to about 2800 cigarettes in 1993, death from lung cancer has reached a high among males at the rate of 74.9/100,000/year and among females at the rate of 28.5. However, in the younger cohorts, the lung cancer death rate is decreasing in both men and women. In this overview we discuss the steeper increase during recent decades of lung adenocarcinoma incidence compared with squamous cell carcinoma of the lung. In 1950, the ratio of these two major types of lung cancer in males was about 1:18; today it is about 1:1.2-1.4. This overview discusses two concepts that are regarded as contributors to this change in the histological types of lung cancer. One factor is the decrease in average nicotine and tar delivery of cigarettes from about 2.7 and 38 mg in 1955 to 1.0 and 13.5 mg in 1993, respectively. Other major factors for the reduced emission of smoke relate to changes in the composition of the cigarette tobacco blend and general acceptance of cigarettes with filter tips; the latter constitute 97% of all cigarettes currently sold. However, smokers of low-yield cigarettes compensate for the low delivery of nicotine by inhaling the smoke more deeply and by smoking more intensely; such smokers may be taking up to 5 puffs/min with puff volumes up to 55 ml. Under these conditions, the peripheral lung is exposed to increased amounts of smoke carcinogens that are suspected to lead to lung adenocarcinoma. Among the important changes in the composition of the tobacco blend of the U.S. cigarette is a significant increase in nitrate content (0.5% to 1.2-1.5%), which raises the yields of nitrogen oxides and N-nitrosamines in the smoke. Furthermore, the more intense smoking by the consumers of low-yield cigarettes increases N-nitrosamines in the smoke 2- to 3-fold. Among the N-nitrosamines is 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a powerful lung carcinogen in animals that is exclusively formed from nicotine. This organ-specific tobacco-specific nitrosamine (TSNA) induces adenocarcinoma of the lung. All of these factors, the more intense smoking, the deeper inhalation of the smoke, and the increased yields of N-nitrosamines in the smoke of low-yield cigarettes, are considered major contributors to the drastic increase in lung adenocarcinoma among cigarette smokers in recent years. This overview also discusses the differences in the major lung cancer types in female compared with male smokers as well as the likely underlying factors for increased lung cancer risk among African Americans compared with that among white Americans. Although the only sure way to prevent smoking-related diseases is giving up the tobacco habit, there must be a measure of protection for those who cannot accomplish this. Therefore, setting upper permissible limits of tar levels for the smoke of U.S. cigarettes, similar to strategies already taken in Western Europe, should be considered.

230 citations


Journal Article
TL;DR: P53 and erbB-2 expression in patients with localized adenocarcinoma and associated p53 status with survival was examined to allow the development of a model of cancer recurrence in this most common lung cancer.
Abstract: Historical information and pathological material from 150 consecutive patients with localized adenocarcinoma of the lung was collected to evaluate oncogene expression of erbB-2 and p53, and erbB-2 gene amplification. Pathological material after resection was reviewed to verify histological staging, and patient follow-up was complete in all cases for at least 68 months. Immunohistochemistry of erbB-2 (HER-2/neu) and p53 oncogene expression was performed on two separate paraffin tumor blocks for each patient with normal lung as control. Gene amplification of erbB-2 was measured after DNA extraction from 20-micrometer sections of erbB-2-positive and -negative tumors. All analyses were blinded and included Kaplan-Meier survival estimates with Cox proportional hazards regression modeling. Two adequate blocks of tumor and normal lung were available for 138 (92%) patients. Immunohistochemical identification of expression of p53 was observed in 49 (37%) patients and erbB-2 in 17 (13%) patients. DNA dot blot analyses were performed on 17 erbB-2-positive and 13 randomly selected erbB-2-negative tumors. There was 1 (6%) of 17 erbB-2-positve tumors with 4-fold erbB-2 gene amplification. Actual 5-year survival was 63% and actuarial 10-year survival was 59% for the entire population of 150 patients. Significant univariate predictors (P 3 cm, poor differentiation, visceral pleural invasion, and p53 expression. Multivariate analysis associated symptoms and p53 expression as independent factors with decreased survival. Thus, this project examined p53 and erbB-2 expression in patients with localized adenocarcinoma and associated p53 status with survival. Multicenter collection of data should allow the development of a model of cancer recurrence in this most common lung cancer.

71 citations


Journal Article
TL;DR: The data suggest that a selective association exists between the AA polymorphism and adenocarcinoma of the lung and that a lower dose of tobacco is sufficient to exert carcinogenic effects on the adenomatous tissue of subjects carrying the AA SNP.
Abstract: A case-control study on lung cancer in African-Americans has been conducted to assess whether a novel African-American-specific polymorphism in the CYP1A1 gene increases the susceptibility to tobacco-related lung cancer. The prevalence of the AA RFLP was 17.1% in the DNA extracted from archived tissue blocks from 76 incident cases of lung cancer, and was 16.3% in peripheral blood lymphocyte DNA of 123 healthy African-American volunteers recruited from a community in the eastern United States. The analysis by histological type showed an association between adenocarcinoma (AC) of the lung and the AA RFLP (odds ratio, 2.6; 95% confidence interval, 1.1–6.3). One homozygous variant subject was present among the AC cases. The risk of AC in subjects who both smoke and carry the AA RFLP was more than double, in comparison to subjects who only smoke (relative interaction magnitude under the additive model, 24%). The mean value of pack-year in AC with the polymorphism was 5.0 ± 2.5 and in AC without the polymorphism was 37.2 ± 6.5 ( P < 0.05). Our data suggest that a selective association exists between the AA polymorphism and adenocarcinoma of the lung and that a lower dose of tobacco is sufficient to exert carcinogenic effects on the adenomatous tissue of subjects carrying the AA polymorphism.

70 citations


Journal ArticleDOI
TL;DR: HPV-18 may play an important role in the development and progression of cancer in some cases of both squamous cell carcinoma and adenocarcinoma of the lung.
Abstract: To provide an accurate evaluation of the association of human papillomavirus (HPV) with lung cancer, 36 cases of lung cancer were analysed for HPV DNAs by polymerase chain reaction (PCR) with dot-blot and Southern blot analyses, and for the transcripts from the E6-E7 transforming region by in situ hybridisation (ISH). HPV-18 DNA was detected in three (8%) of 36 specimens; histologically, in one (10%) of 10 squamous cell carcinomas and two (9%) of 22 adenocarcinomas. Neither HPV-16 nor -33 DNA was detected in any cases examined. Expression of E6-E7 mRNA was confirmed in the cases which contained, HPV-18 DNA. HPV-18 may play an important role in the development and progression of cancer in some cases of both squamous cell carcinoma and adenocarcinoma of the lung.

64 citations


Journal Article
TL;DR: The results do not confirm an earlier report that this CYP1A1 polymorphism may be an important risk factor for adenocarcinoma of the lung in African-Americans and no important associations were observed upon stratification by several risk factors for lung cancer.
Abstract: The possible association between lung cancer and a polymorphism of the CYP1A1 gene specific to African-Americans was examined using peripheral blood DNA from 144 incident cases of lung cancer and 230 population controls with detailed data on smoking and other risk factors for the disease. The CYP1A1 variant allele was present in 15.2% of controls and 16.7% of cases. The smoking-adjusted odds ratio for the presence of the variant allele in relation to lung cancer risk overall was 1.3 (95% confidence interval, 0.7–2.4). According to histological type, the strongest association was observed for squamous cell carcinoma (odds ratio, 2.1), but this result was compatible with chance (95% confidence interval, 0.8–5.9). Adenocarcinoma was not materially associated with the presence of the variant allele (odds ratio, 1.3; 95% confidence interval, 0.5–3.2). No important associations were observed upon stratification by several risk factors for lung cancer, including smoking history, occupational exposures to asbestos and motor vehicle exhaust, or low intake of the micronutrient antioxidants β-carotene, vitamin E, or vitamin C. These results do not confirm an earlier report that this CYP1A1 polymorphism may be an important risk factor for adenocarcinoma of the lung in African-Americans.

64 citations


Journal ArticleDOI
TL;DR: It was found that poorly differentiated adenocarcinoma showed significantly high frequencies of genotypes C and Val/Val, which have been found to be 'susceptible' in squamous cell carcinoma of the lung.
Abstract: We have previously reported on an association of genetic susceptibility to squamous cell carcinoma of the lung with two polymorphisms of the CYP1A1 gene, an MspI polymorphism and an isoleucine-valine (Ile-Val) polymorphism. We report here that the two CYP1A1 polymorphisms were associated with current or ex-smokers with adenocarcinoma of the lung. We first compared smoking status of the patients by differentiation grades of adenocarcinoma. Proportion of current or ex-smokers and their cigarette consumption was the highest among the poorly differentiated. Second, the two polymorphisms of CYP1A1 were examined among current or ex-smokers with three differentiation grades, and we found that poorly differentiated adenocarcinoma showed significantly high frequencies of genotypes C and Val/Val, which have been found to be 'susceptible' in squamous cell carcinoma of the lung. Third, a case-control study was carried out to estimate the genetic risk for CYP1A1 genotypes to differentiation grades, selecting only current or ex-smokers in patients and controls. Current or ex-smokers with 'susceptible' genotype C or Val/Val were at significant risk, with an odds ratio of 3.25 or 3.22 (95% confidence interval (CI), 1.40-7.56 or 1.00-10.32) for adenocarcinoma as a whole, respectively. The odds ratio increased to 4.51 or 4.09 (95% CI, 1.73-11.78 or 1.12-14.91) for poorly differentiated, while the odds ratios for other differentiated grades were not significant. Finally, a relation of the genetic risk to cigarette dose levels was evaluated.

50 citations


Journal ArticleDOI
TL;DR: The expression of multidrug‐resistance‐associated protein (MRP) was assessed in various types of untreated lung cancer using an immunohistochemical technique and its expression was associated with the degree of glandular differentiation of the tumor.
Abstract: The expression of multidrug-resistance-associated protein (MRP) was assessed in various types of untreated lung cancer using an immunohistochemical technique. MRP was abundantly expressed in 28 of 59 adenocarcinoma specimens (47%) and its expression was associated with the degree of glandular differentiation of the tumor. MRP expression in well-differentiated adenocarcinomas (56%) was higher than in poorly differentiated adenocarcinomas (22%) (p < 0.01). lower--20% in squamous-cell carcinomas, 20% in large-cell carcinomas and 0% in small-cell carcinomas and carcinoids. RT-PCR showed that the MRP-positive adenocarcinomas and squamous-cell carcinomas expressed mrp mRNA significantly. Immunoelectron microscopically, MRP was localized in the plasma membrane and rough endoplasmic reticulum. It is thus important to take MRP into account when considering chemotherapy for lung cancers because levels of mdr I gene product, another multidrug-resistance gene family, are low in untreated lung cancers.

43 citations


Journal Article
TL;DR: The ratio of adenocancinoma to squamous cell carcinoma has been steadily increasing; in white males, this ratio was 1 :2.3 from 1 969 to 1 971 but 1 :1 .4 from 1 1 984 to 1 186.
Abstract: Time Trends in Lung Cancer Incidence Susan Devesa (National Cancer Institute) presented lung cancer incidence data for the period 1969-i986 for five geographic areas (Atlanta, GA; Connecticut; Detroit, Ml; Iowa; San Francisco, CA; and Oakland, CA) covering 7% of the United States population. Overall, the rate of lung cancer increased 3%/year from 38.6 to 58.4/1 00,000 personyears during this period. The mate of lung cancer was highest among black men, followed by white men, while mates among women were considerably lower. Among men, squamous cell carcinoma was the most frequent cell type, followed by adenocancinoma and small cell carcinoma. Among women, however, adenocancinoma was the most frequent cell type. On the basis of SEER data for the period 1 983-i 987, for both sexes and all races combined, adenocarcinoma accounted for 31.5% of all lung carcinomas with a rate of 1 6.7/1 00,000 person-years, exceeding that of 1 5.3 for squamous cell carcinoma. Cohorts at highest risk for adenocancinoma were born somewhat later than those at highest risk for squamous cell carcinoma. Women at highest risk were born later than men at highest risk for both cell types. Adenocancinoma was the most frequent type of lung carcinoma among black men under age 50, white men under age 60, black women under age 65, and white women of all ages. The ratio of adenocancinoma to squamous cell carcinoma has been steadily increasing; in white males, this ratio was 1 :2.3 from 1 969 to 1 971 but 1 :1 .4 from 1 984 to 1 986. These data suggest that exposure and mechanisms may vary by histological type.

41 citations


Journal ArticleDOI
TL;DR: In this article, a cohort of 137 patients with completely resected stage I or II adenocarcinoma of the lung was observed from the time of operation; the metastatic pattern determined at autopsy is described in relation to clinical, histologic, and laboratory variables.

Journal Article
TL;DR: The rare instance of adenocarcinoma of the lung that appeared concurrently with a biopsy proven giant cell temporal arteritis in a 45-year-old woman is described.
Abstract: The rare instance of adenocarcinoma of the lung that appeared concurrently with a biopsy proven giant cell temporal arteritis in a 45-year-old woman is described. The lung cancer (without lymph node metastases) was resected, and the temporal arteritis treated with prednisone in the standard dosage regimen. At 36 months followup, she was well with no signs of recurrence or metastases of the lung cancer, nor any recrudescence of temporal arteritis or polymyalgia rheumatica symptoms. This unusual association of lung cancer and temporal arteritis in a young woman, most probably a chance occurrence, has not been previously reported.

Journal ArticleDOI
01 Aug 1995
TL;DR: In primary adenocarcinoma of the lung loss of CD44 expression is associated with less favorable outcome and may indicate a more aggressive neoplasm, and CD44 may be a useful prognostic marker in lung carcinoma.
Abstract: Aims-To determine whether expression of CD44 in neoplasia is associated with tumour grade, stage and prognosis.Methods-The immunohistochemical expression of CD44 was evaluated using the mouse antihuman monoclonal antibody 3G12 which recognises regions shared by all CD44 isoforms to determine whether expression in formalin fixed, paraffin wax embedded tissue correlates with tumour grade, stage or survival in adenocarcinoma of the lung. Thirty one adenocarcinomas of the lung, 16 T2N0 and 15 T2N1, and their nodal metastases were studied.Results-Of the 31 tumours, 25 were positive for the CD44 antigen. CD44 expression correlated with tumour grade, in that intense staining was seen only in moderately and/or poorly differentiated tumours. CD44 did not correlate with nodal status, tumour size, pleural invasion, angiolymphatic invasion, or host inflammatory response, but did correlate with survival. A median survival of 46 months was observed in patients with moderate to strong CD44 expression compared with 24 months for those with no or weak expression. Nine patients were alive without evidence of disease at a median follow up of 61 months. Six (66%) of these nine patients had strong CD44 expression. This contrasts with strong expression in only three (17%) of the 17 patients dying with a median survival of 28 months.Conclusion-In primary adenocarcinoma of the lung loss of CD44 expression is associated with less favorable outcome and may indicate a more aggressive neoplasm. CD44 may be a useful prognostic marker in lung carcinoma.

Journal ArticleDOI
15 May 1995-Cancer
TL;DR: A flow cytometric study using paraffin embedded archival material from 160 patients who underwent surgical resection from 1982 to 1991 to assess the prognostic value of DNA ploidy in adenocarcinoma of the lung.
Abstract: Background. To assess the prognostic value of DNA ploidy in adenocarcinoma of the lung, the authors performed a flow cytometric study using paraffin embedded archival material from 160 patients (109 [68%] with aneuploid lesions, 51 [32%] with diploid lesions) who underwent surgical resection from 1982 to 1991. Methods. The proportion of DNA aneuploid tumors increased as the disease stage advanced, from 35 of 63 (55.5%) with Stage 1 disease to 15 of 20 (75.0%) with Stage 2 disease, to 40 of 53 (75.5%) with Stage 3a disease, to 19 of 24 (79.2%) with Stage 3b disease. However, this trend was not statistically significant. Comparison of the survival time of the 160 patients with adenocarcinoma of the lung with a median follow-up of 7.8 years revealed that patients with diploid tumors had significantly longer survival than did those with aneuploid tumors (P < 0.01). Results. Examination by stage showed that patients with Stage 1 disease with diploid tumors had significantly longer survival times than did those with aneuploid tumors (P < 0.05) but that there were no significant differences in clinical outcome in patients with Stage 2, 3a, and 3b diploid tumors. Conclusions. Analysis of aneuploid versus diploid DNA content in patients with Stage 1 adenocarcinoma of the lung is concluded to be useful in evaluating clinical outcome and prognosis. Cancer 199575 :2461-5.

Journal ArticleDOI
TL;DR: The presence of PTHrP in a very high percentage of malignant mesotheliomata indicates the value of including it in the panel of antibodies utilized in the differential diagnosis of mesotHelioma.
Abstract: The distinction between pleural malignant mesothelioma and pulmonary adenocarcinoma remains a problem in diagnostic histopathology Parathyroid hormone-related protein (PTHrP) has been demonstrated in the neoplastic cells of malignant mesotheliomata, using a polyclonal antiserum raised to synthetic PTHrP(1-16) In a series of 44 malignant mesotheliomata and 44 cases of pleural adenocarcinomata, PTHrP was localized immunohistochemically in 84 per cent of the mesotheliomata and in 11 per cent of the pleural adenocarcinomata Normal and reactive mesothelium did not contain detectable PTHrP The presence of PTHrP in a very high percentage of malignant mesotheliomata indicates the value of including it in the panel of antibodies utilized in the differential diagnosis of mesothelioma

Journal ArticleDOI
TL;DR: The development of an unusual lung tumor in a patient with FAP, a condition associated with other extracolonic tumors, suggests that there may be an association between the two conditions.
Abstract: A 43-year-old man presented with a lung nodule 19 years after undergoing a total colectomy for familial adenomatous polyposis (FAP). There had been no evidence of malignant transformation in the colectomy specimen, and current gastrointestinal investigation did not reveal evidence of tumor. Pathological analysis of the lung nodule demonstrated adenocarcinoma of the lung of the fetal type. This is the first reported case of a lung neoplasm in a patient with FAP. The development of an unusual lung tumor in a patient with FAP, a condition associated with other extracolonic tumors, suggests that there may be an association between the two conditions.

Journal ArticleDOI
TL;DR: It has been postulated that evaluation of malignant disease and its behavior might be simplified by measuring nuclear DNA and the protein contents of tumors, contributing to disease control.

Journal Article
TL;DR: Investigation of a 56-year-old man with lung cancer which secreted human growth hormone showed poorly differentiated adenocarcinoma with no evidence of lymph node metastasis and a group of the tumor cells demonstrated a specific reaction for anti-hGH antibody.
Abstract: The authors reported a case of a 56-year-old man with lung cancer which secreted human growth hormone (hGH) On admission, he had clubbed fingers and gonalgia without complaining cough or sputum Serological examination revealed a high level of hGH which was 227 ng/ml (normal < 146) Right upper lobectomy was performed in February, 1994 It returned to the normal level after resection of the tumor Gonalgia was improved but he still had clubbed fingers after operation Histological examination of the tumor shows poorly differentiated adenocarcinoma with no evidence of lymph node metastasis Immunohistochemical study showed that a group of the tumor cells demonstrated a specific reaction for anti-hGH antibody

Journal Article
TL;DR: High-resolution cytometry may be of value in predicting the biologic behavior of adenocarcinoma cases, especially in stage I/II, where aggressive cancer cells belonging to stage III/IV could be identified.
Abstract: Touch preparations from 60 cases of T1 adenocarcinoma were analyzed using a high-resolution, automated image cytometer. These cases were divided according to pathologic stage: stage I, 31; stage II, 3; stage III, 19; and stage IV, 7. For each nucleus 57 features were analyzed, and using a linear combination of three texture features describing the DNA distribution in the cell nucleus (TARL, ODMAX and FAREA1), aggressive cancer cells belonging to stage III/IV could be identified. The best discrimination between the stages was achieved when the frequency of aggressive cancer cells was 48%; the correct classification rate was 77%. Using this criterion, 22 of 27 patients (81%) who died of cancer within five years after surgery were correctly predicted. These results suggest that high-resolution cytometry may be of value in predicting the biologic behavior of adenocarcinoma cases, especially in stage I/II.

Journal ArticleDOI
TL;DR: Investigation of the prognostic value of the proliferating cell nuclear antigen (PCNA) expression in non-small cell lung carcinomas found no correlation was found between extent of tumors or metastasis and expression of PCNA, and multivariate analyses of all patients showed a trend that those with high proliferating tumors had shorter survival times.
Abstract: The aim of the study was to investigate the prognostic value of the proliferating cell nuclear antigen (PCNA) expression in non-small cell lung carcinomas (NSCLC) Two hundred and sixteen patients with previously untreated NSCLC entered into this investigation For assessment of PCNA expression the streptavidin-biotinylated peroxidase complex method was performed using imnuunohistochemistry and Mab PC10 The tumors were scored for the percentage of PCNA-positive cells (low proliferative activity less than or equal to 25%; high proliferative activity >25%) Univariate analyses of all patients showed a trend that those with high proliferating tumors had shorter survival times than those with lower proliferating tumors Similar results were obtained when the analysis was restricted to squamous cell carcinomas Patients with adenocarcinomas and with high proliferating tumors had significantly shorter survival times than those with low proliferating tumors (p=0028) No correlation was found between extent of tumors or metastasis and expression of PCNA The multivariate analysis including age, sex, extent of tumors and metastasis as well as PCNA revealed a highly significant influence of extent of tumors (p=0007) and metastasis (p=0003) whereas all other factors including PCNA were of no significant influence


Journal Article
TL;DR: It was proven that the appearance of central fibrosis was significantly related to positive stain for TGF-beta in T1 pulmonary adenocarcinoma.
Abstract: Transforming growth factor-beta (TGF-beta) is known as the growth factor that stimulates the multiplication and accumulation of extracellular matrix. Recently, TGF-beta also has been found to have the ability to control the growth and metastatic potential of cancer cells. It is known that central fibrosis frequently occurs in pulmonary adenocarcinoma and the prognosis becomes poorer as fibrosis become more hyalinized. To estimate the role of TGF-beta in the formation of central fibrosis in pulmonary adenocarcinoma and its influence on the prognosis of patients with pulmonary adenocarcinoma, we performed an immunohistochemical study of TGF-beta in 51 cases of T1 pulmonary adenocarcinoma. Positive stain for TGF-beta was shown in 31 cases, and negative stain was shown in 20 cases. In patients with Stage I, T1 pulmonary adenocarcinoma, the post operative survival curve was compared between positive and negative cases of TGF-beta, and the result showed a tendency toward poorer prognosis in positive cases of TGF-beta. Twenty-four of 51 cases of T1 pulmonary adenocarcinoma had central fibrosis. Twenty of 24 cases with central fibrosis showed positive stain for TGF-beta. It was proven that the appearance of central fibrosis was significantly related to positive stain for TGF-beta in T1 pulmonary adenocarcinoma. According to these results, it is suggested that TGF-beta plays some role in the formation of central fibrosis in pulmonary adenocarcinoma and TGF-beta is possibly a prognostic factor for patients with pulmonary adenocarcinoma.

Journal ArticleDOI
TL;DR: The Thin slice CTにて腫瘍の微細な石灰化を認めた場合その診断を考えるうえで極めて興味深い症例であった.
Abstract: 転移リンパ節に著明な石灰化を認めた稀な気管支腺型肺腺癌の症例を経験した. 患者は32歳男性, 検診の胸部X線写真で右肺の異常陰影を指摘された. 胸部conventionalCT上右肺門から両側縦隔に及ぶ比較的均一な石灰化リンパ節を認めたが腫瘍には石灰化を認めなかった. Thin slice CTにて腫瘍の微細な石灰化とリンパ節の石灰化が微細で不規則であることがわかり腫瘍のリンパ節転移を疑い右中下葉切除及び両側縦隔郭清を行った. 病理では腫瘍は砂瘤体を伴う気管支線型腺癌であり, 切除した石灰化リンパ節の全てに腫瘍の転移を認めた. 肺の腫瘤性病変や所属リンパ節の石灰化を認めた場合その診断を考えるうえで極めて興味深い症例であった. 肺癌症例における石灰化リンパ節の取扱いに関して多くの示唆を与える症例と考え報告した.

Journal Article
TL;DR: Results suggest that expression of sialyl-Lewisx antigen in adenocarcinoma of the lung may be correlated with nodal or distant metastasis.
Abstract: We investigated the immunohistochemical expression of three carbohydrate antigens, sialyl-Lewisa, sialyl-Lewisx and sialyl-Lewisx-i, in human lung cancer tissues using monoclonal antibodies, 2D3, SNH3 and FH6, respectively, and compared the expression rate of these three antigens with clinical and pathologic findings. The expression rate of all the three antigens in adenocarcinoma was higher than that in squamous cell carcinoma and that of sialyl-Lewisx was highest in adenocarcinoma. Sialyl-Lewisx antigen was expressed in all cases of positive nodal metastasis or postoperative distant metastasis in adenocarcinoma. In squamous cell carcinoma, however, there was no relationship between the expression rate of sialyl-Lewisx antigen and nodal or distant metastasis. These results suggest that expression of sialyl-Lewisx antigen in adenocarcinoma of the lung may be correlated with nodal or distant metastasis.

Journal ArticleDOI
TL;DR: An adenocarcinoma cell line was established from pleural effusion of a 67-year-old woman and designated as TK-SA, which demonstrated resistance of the cell line to Cis-platin (CDDP), Cyclophosphamide (CPM) and Tegafur/Uracil (UFT).
Abstract: MIKI, M., ISAWA, T., TESHIMA, T., ANAZAWA, Y., MAHMUD, A.M. and NUKIWA, T. Establishment of a Cell Line from an Adenocarcinoma of the Lung Producing Carcinoembryonic Antigen (CEA) and CAJ9-9. Tohoku J. Exp. Med., 1995, 175 (4), 269-278 - An adenocarcinoma cell line was established from pleural effusion of a 67-year-old woman and designated as TK-SA. The population doubling time of the cells was 100.4hr. Chromosomal analysis revealed the TK-SA to have human aneuploid chromosomes with a near-triploid mode. Ultrastructurally, the TK-SA was compatible with adenocarcinoma. The cell line was highly tumorigenic. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide dye assay demonstrated resistance of the cell line to Cis-platin (CDDP), Cyclophosphamide (CPM) and Tegafur/Uracil (UFT). High carcinoembryonic antigen (CEA) and CA19-9 levels were similar in patient's serum and conditioned medium.


Journal ArticleDOI
TL;DR: It is suggested that in a proportion of cases of Hodgkin’s disease, EBV and proteins of the bcl-2 family are involved in the pathogenesis of the disease.
Abstract: expressed in EBV + Hodgkin’s disease. Moreover, they suggest a possible role for the bak gene product in Hodgkin’s disease. Together, these findings suggest that in a proportion of cases of Hodgkin’s disease, EBV and proteins of the bcl-2 family are involved in the pathogenesis of the disease. To further clarify the pathogenetic role of EBV and the bcl-2 family of proteins it is necessary that bcl-2, bcl-x and bak expression should be investigated in relation to the presence of EBV in parallel in a large number of Hodgkin’s disease cases.


Journal ArticleDOI
01 Aug 1995-Ejso
TL;DR: The data suggest that growth factors might be related to the biological malignancy of tumours with a high cell proliferation, as well as the 5-year survival rates of patients with high-GF and low-GF, and the cases of low-AgNORs.
Abstract: We examined immunohistochemically 111 cases of primary adenocarcinoma of the lung, for transforming growth factor α (TGF α ) or epidermal growth factor (EGF), and argyrophilic nucleolar organizer regions (AgNORs). The presence of more than 75% positive cells for both growth factors was designated as a high-GF, while all others were considered to be a low-GF. If AgNORs counts were more than 5.00, it was considered to be a high-AgNORs group, while less than 5.00 was designated as a low-AgNORs group. In our 111 examined specimens, there were 51 (46%) cases of high-GF, and 64 (58%) with high AgNORs. The 5-year survival rates of the patients with a high-GF and low-GF were 34% and 57% ( P P P

Journal ArticleDOI
TL;DR: This Phase II study evidenced a poor response rate for these regimes on adenocarcinoma and large cell undifferentiated carcinoma of the lung.