Showing papers on "Large cell published in 1993"

Radiation therapy alone for stage I non-small cell lung cancer

Abstract: Purpose: This paper is a retrospective analysis of patients with clinical Stage I non-small cell carcinoma of the lung treated with definitive radiation therapy alone. The results of therapy, patterns of failure and the relationship of technical aspects of the delivery of radiotherapy to outcome are presented. Materials and Methods: From 1980 through 1990, 53 patients with Stage I non-small cell lung cancer were treated with definitive radiation therapy alone at the Radiation Oncology Center of the Mallinckrodt Institute of Radiology and its affiliated hospitals. All patients had a pathologic diagnosis of non-small cell lung cancer and were not candidates for surgical resection because of either patient refusal (10 patients), poor performance status (5 patients), or premorbid medical problems (38 patients). The median age was 73 years. Histologic cell type included squamous (32), adenocarcinoma (11), large cell (4), and unclassified non-small cell (6). Initial tumor size was s 3 cm in 23 patients, between 3 and 5 cm in 13 patients and ≥ 5 cm in 17 patients. Diagnostic staging varied during the study period. All patients had chest X-rays and computed tomography scans of the chest. A majority had liver and bone scans, but only four underwent mediastinoscopy. The radiation therapy was of megavoltage energy in all patients, with a median primary prescription tumor dose of 63.2 Gy. Survival was measured from the date radiation therapy was initiated. Results: The actuarial overall survival rate for the entire group was 19% at 3 years and 6% at 5 years, with a median survival time of 20.9 months. Of the 49 deaths, 35 died of lung cancer; 13 died of intercurrent illness, and one died of pancreatic cancer, which made the actuarial cause-specific survival 33% at 3 years and 13% at 5 years. The actuarial 3-year disease-free survival was 33%. Local primary tumor progression occurred in 22 patients, resulting in a 51% 3-year actuarial freedom from local progression. An additional four patients failed in regional lymph nodes that were included in the original treatment portals. Multivariate analysis found only T stage to be associated with overall survival ( p = .02). However multivariate analysis showed age as a prognostic factor to be approaching statistical significance ( p = .07). Patients under 70 years of age showed an increased survival rate compared to patients over 70 years. Radiation therapy doses ≥ 65 Gy appeared to result in a decreased proportion of patients dying of lung cancer with no apparent increase in either acute or long-term complication rates. Conclusion: Results of definitive radiation therapy for inoperable Stage I non-small cell lung remain inferior to surgical therapy. Potential methods to improve local control with radiotherapy are discussed.

Nasal lymphomas in Peru. High incidence of T-cell immunophenotype and Epstein-Barr virus infection.

Abstract: The incidence of non-Hodgkin's lymphoma of the nasal region is much higher in Peru than in the United States and is similar to the incidence of sinonasal lymphomas in Asian countries. To characterize these lymphomas, we evaluated the clinical, morphologic, and immunohistochemical features of 14 cases and also analyzed the cases for Epstein-Barr virus (EBV) RNA using a sensitive and specific in situ hybridization method. Morphologically, the cases consisted of nine large cell immunoblastic lymphomas, one diffuse mixed cell lymphoma, one diffuse small cleaved lymphoma, one small noncleaved lymphoma, and two cases unclassifiable in the Working Formulation. Eleven cases demonstrated evidence of T lineage, two were of B lineage and one of indeterminate immunophenotype. In 13 of the lymphoma cases including all of the T-cell lymphomas, EBV RNA was detected in a high percentage of cells. Double-labeling immunohistochemical and in situ hybridization studies identified CD43 positivity in the cells labeling for EBV RNA. Much smaller amounts of EBV RNA were detectable in six of eight control benign nasopharyngeal biopsy specimens, and two were completely negative. These findings are similar to the prevalence of EBV-positive T-cell lymphomas in Asian countries and differ from the findings of the more common EBV-negative B-cell nasal lymphomas in the United States. These findings suggest that EBV plays a role in the development of nasal T-cell lymphomas and that the incidence of EBV infection may explain the reported "East-West" difference in the incidence of nasal T-cell lymphomas.

Epstein-Barr virus-latent gene expression and tumor cell phenotype in acquired immunodeficiency syndrome-related non-Hodgkin's lymphoma. Correlation of lymphoma phenotype with three distinct patterns of viral latency.

Abstract: We investigated 49 acquired immunodeficiency syndrome-related lymphomas (ARLs) for Epstein-Barr virus (EBV) by Southern blotting and in situ hybridization and, in positive cases, used cryostat immunohistology to compare EBV-latent gene expression (EBV encoded small RNA-1 [EBER-1], EBV nuclear antigen-2 [EBNA-2], latent membrane protein-1 [LMP-1] and host cell immunophenotype (CD11a, CD18, CD54, CD58, CD21, CD23, CD30, CD39, CDw70, immunoglobulin) patterns with those reported in other EBV infections. EBV+ immunoblast-rich/large cell ARLs (n = 22) showed three patterns of latency: broad (EBER+EBNA-2+/LMP-1+; n = 9), reminiscent of a lymphoblastoid cell line phenotype; restricted (EBER+/EBNA-2-/LMP-1-; n = 6), similar to endemic Burkitt's lymphoma; and intermediate (EBER+/EBNA-2-/LMP-1+; n = 7), a pattern rarely described in vitro but seen in certain EBV-related malignancies. EBNA-2 expression was associated with extranodal lymphomas. EBV+ Burkitt-type ARLs (n = 11) usually showed the restricted latency pattern (n = 8), but some expressed the intermediate form (n = 3). Adhesion (CD54, CD58) and activation (CD30, CD39, CDw70) molecule expression varied with morphology (immunoblast-rich/large cell versus Burkitt-type), but was not independently correlated with EBV-positivity. CD30 and LMP-1 expression were associated. ARLs show heterogeneity regarding both the presence of EBV and latency pattern. Comparison of these phenotypically distinct lymphoma groups with known forms of EBV infection provides clues to their possible pathogenesis.

Carcinoma and atypical hyperplasia in radial scars and complex sclerosing lesions: importance of lesion size and patient age

Abstract: One hundred and twenty-six radial scars and complex sclerosing lesions from 91 women were examined to determine the incidence of and the clinical and pathological factors associated with the development of carcinoma and atypical hyperplasia within them. There was a clear relationship between the presence of carcinoma and atypical hyperplasia and the size of the lesion. This was not, however, a progressive relationship, there being a cut-off point about 6-7 mm, below which carcinoma was very uncommon and above which it was relatively frequent. A similar relationship was seen with patient age. Carcinoma was not seen in lesions removed from women under 40, was rare in the decade 41-50 and was relatively common above this age but with no further increase in the over 60s. A significantly higher incidence of carcinoma and atypical hyperplasia was encountered in scars detected by mammographic screening and could be explained by lesion size and the ages of the patients from which they were removed. No relationship was found between the presence of carcinoma within radial scars and complex sclerosing lesions and the existence of carcinoma in the residual breast tissue when direct extension was excluded. The carcinomas identified in the scars were of variable type and included small and large cell ductal carcinoma in situ, lobular carcinoma in situ and invasive carcinoma of tubular and ductal types. In situ carcinoma and atypical hyperplasia involved a very variable percentage of the epithelium of the lesions with mean values for ductal carcinoma in situ of 32%, lobular carcinoma in situ 25% and atypical hyperplasia 25%.(ABSTRACT TRUNCATED AT 250 WORDS)

Malignant lymphomas involving the ovary: A clinicopathologic analysis of 39 cases

Abstract: We report 39 patients with non-Hodgkin's lymphoma who initially presented with ovarian enlargement. Fifteen patients had unilateral (10 left, four right, one unknown) and 24 had bilateral ovarian masses. The median size of the tumors was 8 cm (range, 2 to 23 cm). Histologically, using the Working Formulation, 21 lesions (54%) were classified as small noncleaved cell, Burkitt's type; 12 (31%) as large cell (nine diffuse, three focally follicular); three (8%) as diffuse mixed, small and large cell; two (5%) as large cell immunoblastic; and one (2%) as follicular and diffuse small cleaved cell. Twenty-six tumors were analyzed immunophenotypically, 25 (96%) of which were B-cell neoplasms. However, combining histologic and immunohistochemical findings, 37 neoplasms were of B-cell lineage, one diffuse large-cell lymphoma was not analyzed, and one large-cell immunoblastic lymphoma (with features of anaplastic large-cell lymphoma) was of T-cell lineage with an aberrant immunophenotype. On the basis of staging studies and clinical follow-up, we conclude that only four (10%) of the neoplasms in this study most likely arose in the ovary. The primary neoplasms, three diffuse large-cell and one diffuse mixed small- and large-cell, were B-cell neoplasms. Three of four patients with primary neoplasms were apparently cured at last follow-up following surgical excision and chemotherapy. The remainder of the lymphomas in this study, most commonly of small noncleaved cell, Burkitt's type, appear to be systemic tumors that involved the ovaries secondarily. Approximately 40% of patients with systemic neoplasms were alive without evidence of disease at last follow-up.

A large cell-adhesive scatter factor secreted by human gastric carcinoma cells

Abstract: Human gastric carcinoma cell line STKM-1 secretes a large protein that induces scattering of a rat liver epithelial cell line (BRL) into disconnected individual cells in monolayer culture. This cell-scattering factor was purified from serum-free conditioned medium of STKM-1 cells and found to be composed of three disulfide-linked subunits of 140, 150, and 160 kDa. The 140-kDa peptide contains an amino acid sequence homologous to that of the laminin B2t chain. The native protein has an apparent molecular mass of > 1000 kDa and a pI of 5.0. In addition to the cell-scattering activity, the purified protein stimulates attachment of BRL cells to substrate and their migration. Similar effects have been observed toward various cell lines, including nontumorigenic epithelial, endothelial, and fibroblastic cell lines and human cancer cell lines. Similar cell-scattering activity was secreted by human squamous carcinoma and gastric carcinoma cell lines and nontumorigenic epithelial and endothelial cell lines. These results indicate that the protein, named "ladsin," is probably an extracellular matrix protein that regulates cell-cell and cell-substrate interactions and cell migration.

Primary Malignant Lymphoma of the Liver

Abstract: Clinical and pathologic features of 69 cases with primary hepatic lymphoma, 52 reported from Western countries and 17 cases from Japan, were summarized in terms of clinical findings including age and sex, past history, presenting symptoms, and physical findings, diagnostic procedures including imaging techniques and histopathology, and finally therapy and follow-up. The present cases included four patients with an acquired immunodeficiency syndrome and 12 with a history of chronic liver diseases. Histologically, all cases were non-Hodgkin's lymphoma with diffuse large cell type being the most common immunochemically about 80% were B-cell type. Follow-up showed that hepatic lymphoma had a relatively favourable prognosis provided early detection was possible.

Malignant lymphoma of the uterus : report of seven cases with immunohistochemical study

Abstract: Background Uterine lymphoma is a rare disease; therefore, information regarding histologic type, immunophenotype of tumor cells, and etiologic factors are limited Methods Seven patients with uterine lymphoma, three from the corpus and four from the cervix, were collected by a nationwide study in Japan Selection of cases was preferentially made from the “Annual of Pathologic Autopsy Cases in Japan” Results All cases with cervical lymphoma presented with vaginal bleeding Abdominal pain or backache was observed in patients with corpus lymphoma The age ranges of patients with corpus and cervical lymphomas were 46–78 years of age (mean, 63 years) and 30–71 years of age (mean, 53 years), respectively Information about clinical staging was available for six patients; two patients with Stage I, three patients with Stage II, and one patient with Stage III A definite diagnosis of uterine lymphoma was made by biopsy in all cases Total hysterectomy, with or without bilateral salpingo-oophorectomy, was carried out in three patients, and tumor resection was carried out in one patient Adjuvant therapy was given in six cases Follow-up showed that five patients died due to tumor within 1 year of treatment Histologically, all cases were non-Hodgkin lymphoma showing a diffuse pattern of proliferation All but one were diffuse large cell type Immunohistochemistry revealed the tumor cells in all cases were of B-cell nature Expression of HLA-DR antigen was evaluable in four cases, of these three showed an increased expression on the vascular endothelium Conclusions Uterine lymphoma comprises exclusively B-cell type

In vitro establishment of AIDS-related lymphoma cell lines: phenotypic characterization, oncogene and tumor suppressor gene lesions, and heterogeneity in Epstein-Barr virus infection.

Abstract: Lymphoma represents a major source of morbidity and mortality among AIDS patients. AIDS-associated non-Hodgkin lymphomas (AIDS-NHL) are almost invariably B-cell derived, are classified as high or intermediate grade lymphomas, and display three main histologic types: namely, small non-cleaved cell lymphoma (SNCCL), large cell immunoblastic plasmacytoid lymphoma (LC-IBPL), and large cell lymphoma (LCL). Here we report the in vitro establishment of three new AIDS-NHL cell lines (termed HBL-1, HBL-2, and HBL-3) derived from three AIDS-SNCCL patients differing in primary tumor sites and risk factors for HIV infection. The derivation of the cell lines from the original tumor clones was established by immunophenotypic and molecular genetic analysis. These cell lines display clonal immunoglobulin gene rearrangement, express surface immunoglobulin and B-cell restricted markers, and exhibit a phenotype consistent with SNCCL. Monoclonal Epstein-Barr virus infection was found in only one of the cell lines (HBL-1). Cytogenetic analysis demonstrated the presence of a chromosomal translocation involving the c-myc proto-oncogene and an immunoglobulin locus in all three cell lines. The pattern of genetic lesions detected in HBL-1, HBL-2, and HBL-3 reflects that found in primary AIDS-SNCCL and includes activation of the c-myc oncogene as well as inactivation of the p53 tumor suppressor gene. These cell lines should prove useful in studies of the biological, immunological, and viral factors involved in AIDS-associated lymphomagenesis.

Increased expression of the src proto-oncogene in hairy cell leukemia and a subgroup of B-cell lymphomas.

Abstract: The c-src proto-oncogene encodes a M(r) 60,000 phosphoprotein, pp60c-src, with tyrosine-specific protein kinase activity. We have used an immune complex protein kinase assay for pp60c-src to analyze a spectrum of B-cell neoplasms. pp60c-src activity was elevated in all five hairy cell leukemia specimens and in a number of the large cell and immunoblastic lymphomas; neoplasms representing later stages in B-cell development. pp60c-src activity was low in neoplastic cells which correspond to early and intermediate stages in B-cell development (acute and chronic lymphatic leukemia, lymphoblastic lymphoma, small lymphocytic lymphoma). The enhanced pp60c-src activity was associated with high levels of pp60c-src protein. However, increased expression of c-src was not associated with amplification or gross structural rearrangement of the c-src gene. This preliminary study demonstrates elevated levels of pp60c-src protein and tyrosine protein kinase activity in neoplasms corresponding to the later stages of B-cell ontogeny.

Cutaneous manifestations of Epstein-Barr virus—associated T-cell lymphoma

Abstract: Background: In addition to human T-lymphotropic virus (HTLV-I), the Epstein-Barr virus (EBV) has recently been demonstrated to be associated with cutaneous T-cell lymphoma (CTCL). Objective: Our purpose was to investigate characteristic clinicopathologic features of the cutaneous lesions of EBV-associated T-cell malignancies. Methods: Clinical records, laboratory data, and histopathologic sections were reviewed. Freshly frozen tumor tissues were immunophenotyped. Southern blot and in situ hybridization studies were performed to detect the EBV genomes. Results: Ten of 35 CTCL biopsy specimens collected between 1985 and 1992 were found to be EBV-associated. Clonotypic proliferation of EBV genomes was demonstrated in each case, and the atypical T lymphoid cells contained EBV genomes. The cutaneous eruptions of these patients included multiple violaceous papules or nodules, chronic ulcers, and tumors on the trunk or extremities. Three distinct clinicopathologic subgroups could be recognized. The most consistent was the angiocentric T-cell lymphoma or lymphomatoid granulomatosis (type III CTCL) (four cases), presenting with chronic ulcers or violaceous papules. The second group was the T large-cell lymphoma (type II CTCL), Ki-1 antigen (CD30) (positive or negative) (four cases). Three patients with Ki-1− lymphoma had fulminant disease, whereas the remaining Ki-1+ case had a benign course. The third group was the secondary type CTCL (type V CTCL) (two cases), representing systemic EBV-associated T-cell lymphoma. The prognosis was grave. The common features of these EBV-associated CTCLs are resistance to conventional chemotherapy, poor prognosis, and the terminal manifestation of a hemophagocytic syndrome. No EBV genome could be detected in 12 cases of classic CTCL/mycosis fungoides (type I CTCL), or in three cases of HTLV-I-associated adult T-cell lymphoma (type IV CTCL). Conclusion: Three distinct clinicopathologic subtypes of EBV-associated CTCL were recognized, including one additional type of virus-associated CTCL.

Peripheral T-cell lymphoma in childhood and adolescence. A clinicopathologic study of 22 patients.

Abstract: Background. Peripheral T-cell lymphoma (PTCL), although the most common T-cell lymphoma in adults, is relatively rare in childhood, and only small series have been reported. Methods/Results. Twenty-two cases of PTCL were studied that occurred in patients 18 months to 20 years of age. Nine were seen when the condition was diagnosed, and the other 13 were referred after they had relapses. The stage at diagnosis was I or II (45%), III (41%), and IV (14%). Patients with Stage IV disease were younger than those with Stage I or II disease (2.5 versus 14.8 years, P = 0.04). Twelve patients had extranodal disease when the diagnosis was made; the skin was the most common site. Ten tumors were classified as diffuse large cell type; five, as diffuse anaplastic large cell type; and seven, as diffuse mixed cell type. Twenty of the 21 tumors tested were CD30 (Ki-1 or Ber-H2) antigen positive. Of the nine patients seen when the diagnosis was made and treated by the authors, three had a relapse (median, 12 months), a 2-year relapse-free survival (RFS) rate of 61%. For the total group, the RFS was longer for patients older than 12 years of age compared with those who were younger (20 versus 12 months, P = 0.05). Overall, six patients remained in their first complete remission. Sixteen patients had a relapse, and 13 of these underwent bone marrow transplantation (BMT). Six of these remained in complete remission (median, 18 months after BMT). Overall, only 6 of 22 patients died (median survival, > 60 months). Conclusion. It was concluded that aggressive therapy, including BMT for relapses, can provide prolonged disease control in most children with PTCL. Cancer 1993; 71:257-63.

Lung cancer histologic types and family history of cancer. Analysis of histologic subtypes of 872 patients with primary lung cancer.

Abstract: Background. Previous research has demonstrated that there is clustering of cancer among relatives of patients with lung cancer and that women may be at a greater risk than men, regardless of their smoking histories. Methods. The authors conducted a study to test the hypotheses that this predisposition varies by the histologic type of tumor and that women with particular histologic types will report more first-degree relatives with cancer than will men with the same cell type. The analyses were based on 872 patients with histologically confirmed lung cancer who had been admitted to Roswell Park Cancer Institute, Buffalo, New York, between 1982 and 1987. Results. More patients with squamous and large cell carcinomas reported two or more relatives with cancer, and overall, women reported more family history of cancer. Among patients with squamous cell carcinoma, this difference between men and women was significant (P < 0.05). Among patients younger than 57 years, those with squamous cell were the most likely to report a family history of cancer (P < 0.01). A similar trend was observed for smoking. Persons with small cell and squamous cell carcinomas who were nonsmokers or had smoked 1–20 years had three times the risk of a family history of cancer than did those with large cell and adenocarcinomas (odds ratio [OR] = 3.01; confidence interval [ci] = 1.38–6.63), in contrast to those who had smoked more than 20 years (OR = 0.85; ci = 0.62–1.62). Conclusions. Squamous cell carcinoma is most associated with familial clustering of cancer, particularly among women, persons younger than 57 years, and individuals who smoked for fewer than 20 years.

Deficient tumor-infiltrating T-lymphocyte response in malignant lymphoma: relationship to HLA expression and host immunocompetence.

Abstract: Tumor-infiltrating T-lymphocytes (T-TIL) are putative mediators of tumor containment that exhibit unique specificity for autologous tumor cells. The magnitude of T-TIL response in biopsy specimens from patients with B-cell lymphoma has been suggested as an independent predictor of clinical outcome. Since recognition of tumor antigens may occur in association with major histocompatibility complex (MHC) molecules, effective T-TIL tumor immunosurveillance may be limited by either failure to express MHC-encoded recognition structures and/or host T-cell immunocompetence. To further delineate T-cell immunoregulation in B-cell lymphoma, we assessed T-TIL fraction and tumor expression of invariant class I and class II HLA determinants by immunohistochemistry in biopsy specimens. Two distinct clinical cohorts of B-cell lymphoma were investigated to delineate pathogenetic differences in T-TIL response. One group, representing immunodeficient and transplant-related lymphomas, comprised 18 patients with AIDS- or allograft-related lymphoma. The second group comprised 83 consecutive cases of sporadic diffuse large cell (DLCL) lymphoma. Median CD8+ T-TIL was significantly lower (4.9% versus 12.7%) among immunodeficiency-associated lymphoma and the frequency of cases with low (< 6%) CD8+ T-TIL greater (76% versus 23%) (p < 0.0001). None of the immunodeficiency-associated lymphomas demonstrated non-polymorphic HLA loss. Absence of one or more class I or II HLA determinants was found in 13 out of 19 (68%) sporadic DLCL specimens with low CD8+ T-TIL, compared to 20% of cases with higher T-TIL fraction (p = 0.0004). These findings implicate impaired host immunosurveillance in deficient T-TIL response in immunodeficiency-associated B-cell lymphoma, whereas low T-TIL in sporadic cases of DLCL relates to tumor loss of HLA determinants. Strategies to modulate tumor HLA expression or augment antitumor response merit investigation in patients with B-cell lymphoma.

Secretion of a latent, acid activatable cathepsin L precursor by human non-small cell lung cancer cell lines

Abstract: Secretion of pro-cathepsin L, the precursor of a lysosomal cysteine proteinase, has been described for ras-transfected mouse fibroblasts and several human cancer cell lines. The secretion of a latent but stable precursor might be a means for tumor cells to involve this proteinase in extracellular matrix breakdown. Since lung cancer is the leading cause of cancer death in the industrialized countries, we therefore studied the secretion of pro-cathepsin L in 11 human non-small cell lung cancer cell lines (EPLC 32M1, NCI H157, EPLC 272H, U1752, LCLC 103H, LCLC 97TM1, U 1810, NCI H661, NCI H23, NCI H125, and NCI H596) and 8 human small cell lung cancer cell lines (SCLC 22H, NCI H60, NCI H82, NCI H526, NCI H146, NCI H841, NCI H510, and DMS 79). Immunoblot analysis of cell conditioned media showed that latent pro-cathepsin L (M(r) 42 kDa) was secreted in all 11 non-small cell lung cancer cell lines. Three of these cell lines secreted an additional inactive form of cathepsin L of M(r) 24 kDa. In contrast, the 8 small cell lung cancer cell lines did not secrete any detectable cathepsin L-immunoreactive material. Phorbol-12-myristate-13-acetate increased the secretion of pro-cathepsin L in 6 of the non-small cell lung cancer cell lines. The cathepsin L precursor could be activated in vitro at pH 3, accompanied by a shift in molecular mass to 34 kDa. Chicken egg white cystatin prevented the acid activation. Specific antibodies against a synthetic peptide from the pro-sequence of cathepsin L reacted with the nonsmall cell lung cancer cathepsin L precursor. Extracellular pro-cathepsin L may be important in the tumor biology of non-small cell lung cancer and would be a good target for novel diagnostic and therapeutic approaches, since the majority of physiological lysosomal proteinases are contained in intracellular compartments only.

Primary leptomeningeal T-cell lymphoma: a case and a review of primary T-cell lymphoma of the central nervous system.

Abstract: A case of primary leptomeningeal T-cell lymphoma of pleomorphic large cell type is presented. The lymphoma, which was first diagnosed at autopsy, occurred in a 67-year-old man, who had no personal or family history of immunodeficiency disorders. Review of the literature reveals only 13 immunocytochemically well-documented cases of primary T-cell lymphoma in the CNS. In five of these cases the lymphoma was apparently confined to the leptomeninges. The relatively high frequency of leptomeningeal presentation may indicate that this tumor form is more common with primary T-cell lymphoma of the CNS than with B-cell neoplasms.

Demonstration of Epstein-Barr Viral Genomes by In Situ Hybridization in Acquired Immune Deficiency Syndrome-Related High Grade and Anaplastic Large Cell CD30+ Lymphomas

Abstract: From September 1984 through December 1991, of those with human immunodeficiency virus infection seen at the acquired immune deficiency syndrome unit of the Centro di Riferimento Oncologico, Aviano, Italy, 71 patients had systemic non-Hodgkin’s lymphomas. The most frequent histotypes were small noncleaved cell, anaplastic large cell (ALC) CD30/BerH2+, and large cell immunoblastic. In 22 representative cases of these histotypes, including 9 of small noncleaved cell, 9 of ALC CD30/BerH2+, and 4 of immunoblastic non-Hodgkin’s lymphomas, Epstein-Barr virus genetic information was assessed by in situ hybridization and correlated with histologic and immunophenotypic findings. Expression of B-cell associated markers, usually including CD19, CD20, CD22, CDw75, and CD74, was found in 17 of the 22 evaluated cases. All small noncleaved cell and immunoblastic cases and four cases of ALC lymphomas expressed B-cell immunophenotypes, whereas the remaining ALC cases were immunologically undetermined. In situ hybridization detected Epstein-Barr virus in 12 of 22 cases (54.5%). Seven of nine ALC lymphomas were positive, as were three of five small noncleaved cell type (Burkitt’s lymphoma), one of four small noncleaved cell type (non-Burkitt’s variant), and one of four large cell immunoblastic type. The results of this study indicate that Epstein-Barr virus genomes might be identified in more than 50% of the evaluated high grade non-Hodgkin’s lymphomas; this association occurred significantly more often in the small noncleaved cell lymphomas resembling endemic Burkitt’s lymphoma (60%) and with ALC CD30/ BerH2+ lymphomas (77.8%). These findings support the notion that Epstein-Barr virus may play a role in the development of non-Hodgkin’s lymphomas in a proportion of human immunodeficiency virus-infected patients.

Detection of thrombomodulin in human lung cancer cells.

Abstract: Thrombomodulin (TM), which usually exists in vascular endothelial cells and exerts an anticoagulant activity, was detected by Western blot analyses and immunocytochemical staining using three anti-TM monoclonal antibodies in cultured cell lines derived from a squamous cell carcinoma and an adenocarcinoma of the lung, but was not detected in a cell line derived from a small cell carcinoma. Functional assays indicated that TM detected in these cells was functionally active. The presence of TM in 22 specimens of surgically removed lung cancer tissue was also examined by an immunohistochemical method. TM was present along the cell membranes in 4 (36%) of 11 squamous cell carcinomas examined, but was not detected in 10 adenocarcinomas and 1 large cell carcinoma examined. Because TM is identical to fetomodulin, which modulates embryogenesis, the authors have concluded that TM is an oncodevelopmental antigen. The authors have also suggested that functionally active TM on lung cancer cells may modulate cancer cell behaviors in such ways as exhibiting anticoagulant activity.

Expression of dipeptidyl aminopeptidase IV activity in human lung carcinoma.

Abstract: Dipeptidyl aminopeptidase IV (DAP IV) staining was examined in various histological types of lung carcinomas to evaluate this enzyme activity. A total of 45 lung carcinomas were examined for their enzyme activity. Almost all (93.1%) cases of adenocarcinoma were positive for DAP IV activity, whereas all cases of squamous cell carcinoma, small cell carcinoma, large cell carcinoma and carcinoid were negative. DAP IV activity of microsomes in lung carcinomas was significantly higher in papillary adenocarcinomas than in squamous cell carcinomas. These data suggest that DAP IV may be a good marker to distinguish adenocarcinoma from other histological types of lung carcinoma.

OV‐TL 12/30 (keratin 7 antibody) is a marker of glandular differentiation in lung cancer

Abstract: The immunoreactivity of OV-TL 12/30, a monoclonal antibody to keratin 7 was investigated on paraffin-embedded human lung cancer tissues of 61 patients. A modified AEC-immunoperoxidase method with pepsin pre-digestion was used. In normal lung tissue keratin 7 was found in bronchial and bronchiolar epithelium, pneumocytes and compound glands. Squamous metaplasia of the bronchial tree was negative. All 24 squamous cell carcinomas were negative irrespective of grade of differentiation. All differentiation grades of 20 adenocarcinomas including bronchioalveolar carcinomas were positive. Since six large cell anaplastic carcinomas did not react with keratin 7 antibody these tumours are considered to be of squamous cell rather than adenocarcinomatous origin. Small cell anaplastic carcinomas were negative in 10 of 11 cases. Our study demonstrates that this keratin 7 antibody is useful in differentiating between squamous cell carcinoma and adenocarcinoma of the lung and it may be particularly useful in making the correct diagnosis in small lung biopsy specimens.

Prognostic factors in lung cancer based on multivariate analysis.

Abstract: Multivariate analysis was performed on 1,336 patients with lung cancer to determine the prognostic significance of stage, race, gender, age, and treatment in each histologic subtype. The study was designed to establish a subgroup of patients whose survival outcome might be better, based on these factors. On univariate analysis, stage and surgery were significant factors in each histologic subtype. The presence of liver metastases, was an important prognostic factor in all subtypes except large cell carcinoma. However, 131 of 140 patients with large cell carcinoma had liver metastases, and this factor may account for the observation that liver metastases was not a significant prognostic factor. In the multivariate analysis, good prognosis was associated with early stage disease and surgical treatment in all cell types. For a given stage, the improvements in relative risk due to surgery represent both the effect of treatment and the effects of other unmeasured patient characteristics, such as performance status and physiological status, that make the patient a suitable candidate for surgery.