The heterogeneity of cells capable of metastasation has proved to be the greatest obstacle to successful treatment or to prevention of metastatic diseases. This variety appears to be attributable to processes of selection. Cytobiological investigations which are helpful in casting some light at selective mechanisms of metastasation may, perhaps, make substantive contributions to cancer therapy.

Tumor progression and metastasis

Short-Term Tests for Chemical Carcinogens

A systematic review and a meta-analysis were performed on 19 studies on head and neck cancer (HNC) and 21 studies on breast cancer (BC) to evaluate the application of micronucleus (MN) assay as a predictive and prognostic test for cancer risk. In these studies the MN test was applied in peripheral lymphocytes and buccal cells of patients and healthy subjects with family history of cancer. The meta-analysis on MN applied in buccal cells of HNC patients was performed on two subgroups of studies. A significant increase of MN frequency in patients compared to healthy controls was observed for the subgroup on oral cancer (243 cases/370 controls, meta-MR = 4.71 95 %CI:2.75-8.06) and HNC (204 patients/163 controls metaMR=2.28 95 %CI:2.02-2.58). A metaMR = 3.27 (95 %CI:1.41-7.59) was obtained for MN applied in peripheral lymphocytes on HNC (160 cases/160 controls). For BC, the analysis of MN in peripheral lymphocytes showed significantly higher values in patients (n = 761) than in controls (n = 788) (meta-MR1.90 95 % CI:1.44-2.49). No statistically significant increase of baseline MN was detected in studies on groups of healthy subjects with BC family history (n = 224) or with BRCA1/2 mutations (n = 101) with respect to the controls. After ex-vivo challenge with ionizing radiation, the meta-analysis revealed a slightly statistically significant increase in MN only in BC patients (n = 614) compared to controls (n = 622)(meta-MR = 1.11 95 %CI:1.02-1.21); no increase was observed in healthy subjects with BC family history carrying or not BRCA1/2 mutations. Significant difference between BC patients (n = 183) and controls (n = 165) was observed by the meta-analysis of data on MN in buccal cells (MR = 3.89 95 %CI:1.54-9.78). The MN assay in buccal cells has some perspective of clinical application in HNC.

Micronuclei and upper body cancers (head, neck, breast cancers) a systematic review and meta-analysis.

Introduction This study investigated the cellular changes in the mouth of smokeless tobacco (shamma) users among Saudi citizens from the Najran region. Methods Healthy 61 shamma users and healthy 61 non-users participated in this study after informed consent. A mouth swap was taken from each study subject and investigated for cellular changes using a Papanicolaou stain. The results were analyzed using the t-test per cent of the StatPac statistical program. Results Keratinization, binucleation and combined results were associated with shamma use. The number of shamma users with abnormal histology was 14 (22.9%) (p≤0.0001). The shamma types associated with the abnormal cytology were: Suhaily (9/36; p=0.0014), black (2/9; p=0.08), white (2/6; p=0.41), and red (1/1; p=1.00). The percentage of the tissues with abnormal histology decreased with the increase in the duration and frequency of smokeless tobacco use, except for the white shamma which increased with the increase in the frequency. Conclusions Shamma use affected the mouth epithelial cytology of 22.9% of its users. The histological changes were inflammation, keratinization, binucleation, and atypia. The Suhaily smokeless tobacco was associated with the highest percentage of the abnormal cytology results, while the duration and frequency of smokeless tobacco use decreased the number of tissues with abnormal histology.

http://www.tobaccoinduceddiseases.org/pdf-109544-40181?filename=Cytological changes in.pdf

Cytological changes in oral mucosa induced by smokeless tobacco.

South Asian Journal of Cancer ♦ Volume 6 ♦ Issue 2 ♦ April-June 2017 89 Since there is a considerable similarity between the two criteria, using the former criterion is technically not wrong, provided it is fulfilled completely. To conclude, I request the authors to go through their images again and make sure they are compatible with the criterion used. The purpose of this letter is not to highlight an error rather to focus on the appropriate criterion to be used for future studies. Such parameters play a vital role in establishing the validity of the study.

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Complete response with crizotinib in two children with chemotherapy resistant neuroblastoma.

Background: Oral carcinogenesis is a multi-step process. Broadly, oral squamous cell carcinoma (OSCC) can be well-, moderately- or poorly-differentiated, and either keratinizing or non-keratinizing. Most cases are moderately to poorly-differentiated. Precursor lesions (dysplasia) can be categorized into mild, moderate, or severe (carcinoma in situ).In the present study, the pattern of keratin expression in oral squamous cells during carcinogenesis is vividly analysed. Materials and Methods: Samples in the form of scraped and exfoliated cytosmear were collected from the affected sites of the clinically diagnosed 136 oral cancer patients and were immediately fixed in acetoalcohol (1:3). The wet fixed smears were stained by routine Papanicolaou’s staining protocol and Giemsa’s solution. Stained tissues were studied under the microscope. Results: Cytological pleomorphism is a unique feature observed during carcinogenesis. There appears to be a spectrum of degrees of keratinization rather than distinct types, and the degree of keratinization is reflected in the degree of packing and orientation of keratin filaments. It is presumed that alteration in the architectural regularity of the cell membrane is an important aspect of keratinization which leads to cytological pleomorphism during oral carcinogenesis. Conclusion: Pattern of keratinization alongwith cytological pleomorphism in exfoliated epithelial squamous cells has a practical utility in the diagnosis and early detection of oral cancer during carcinogenesis.

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Pattern of Keratinization in Oral Squamous Cells during Carcinogenesis

Chewing and smoking of tobacco as well as drinking of alcohol have been reported as the risk factors for oral cancer. The high incidence of oral cancer in India and gradual increase of oral cancer patients at the Out Patient Department of Acharya Harihar Regional Cancer Center (AHRCC) Cuttack, Odisha (the only Government Hospital of the state dedicated for the treatment of the cancer patients) prompted us to undertake this study. In this hospitalbased case-control study, the genotoxic effect of tobacco and alcohol was evaluated through micronucleus test. The percentage of micronucleated cells were recorded to be the highest in chewer-smoker-alcoholics group (2.86 in males and 3.35 in females) and the least in smokers’ group (0.68 in males and 0.65 in females). The values were found to be statistically significant at 1% level of confidence (Z-test). But, the occurrence of micronucleated cells in higher percentage in non-addicted cancerous group (1.23 in males and 1.20 in females) than the single addicted groups (such as chewers, smokers and alcoholics) indicate the causes of genetic susceptibility followed by oral unhygienic condition and modern life style in food pattern among the people of Odisha. Therefore, it needs special attention for which further investigation is suggested.

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Genotoxicity of tobacco and alcohol on human oral mucosal cells

Aim: During the present investigation, two types of keratinized round cells (KRCs), large keratinized round cells (LKRCs) and small keratinized round cells (SKRCs), were observed in the exfoliated buccal smears of oral cancer patients. Therefore, the aim of the present study was to determine the practical utility of KRCs during difficult diagnosis and in the early detection of oral squamous cell carcinoma (OSCC) through cytomorphometric analysis. Materials and Methods: In a hospital-based case control study, exfoliated scrape smears were collected from 136 patients clinically diagnosed as suffering from pre-cancerous lesions and OSCC and a parallel set of 136 samples were also collected from non-addicted and non-cancerous healthy individuals from different regions of Odisha, and this was considered as the control group. Wet-fixed smears were stained by adopting Papanicolaou's staining protocol and counter-stained with Giemsa's solution. One thousand cells were screened and keratinized round cells along with other cytological atypia were scored. Cytomorphometry was carried out using a computer-assisted Cat Cam 1.30 (1.3 Mega Pixel) microscope camera. The findings were statistically analyzed and interpreted with respect to oral sites, age groups and sexes. Results: Cytomorphometrically, the nucleus to cytoplasmic ratio of the LKRCs was 1:4.7 in males and 1:4.3 in females, and in SKRCs it was calculated to be 1:4.6 in males and 1:5.2 in females. Conclusion: Cellular keratinization, hyperchromasia and increased N/C ratios in both LKRCs and SKRCs indicates the state of malignancy and thus the present finding has a practical value in early detection and diagnosis of OSCC patients.

Cytomorphometric analysis of keratinized round cells in human oral carcinoma

Background: Oral cancer ranks in the top three of all cancers in India, which accounts for over 30% of all cancers reported in the country. The micronucleus test (MNT) is one of the most widely applied short term tests used in genetic toxicology to evaluate the mutagenicity and carcinogenicity. Aims: The present study aims at an in vivo cytogenetic analysis of human oral squamous cell carcinoma and to assess the applicability of MNT in diagnosing early detection of oral carcinoma. Materials and Methods: Exfoliated scrape smears were collected from the clinically diagnosed 136 patients suffering from oral precancerous and cancerous lesions. The wet fixed smears were stained by adopting Papanicolaou's staining protocol and counter-stained with Giemsa's solution. Results: The frequency of micronucleated cells has been observed to be in increasing order with the increase of the age-groups and from control to precancerous to cancerous cases significantly in both sexes. Conclusion: Micronucleus formation in the oral mucosa could be a biomarker of genetic damage and also a potential onco-indicator in the long run of oral carcinogenesis. Therefore, MNT can be applied for the early detection of oral carcinoma in the human being.

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An in vivo cytogenetic analysis of human oral squamous cell carcinoma

Cytopathology of human oral squamous cell carcinoma reveals cytological pleomorphism. In this investigation, cytometry was used in an attempt to analyse the importance of the rare occurrence of keratinized strap cells in the buccal mucosa of human oral neoplasms. A case–control study was undertaken in which exfoliated cytosmears were collected, by scraping, from 136 clinically diagnosed oral cancer patients. Wet fixed cytosmears were stained by use of Papanicolaou’s staining  procedure and counter-stained with Giemsa’s solution. One thousand cells were screened, and keratinized strap (Anitschkow) cells (KSC-A) and other cytological atypias were counted. Cytomorphometry was performed by use of a computer-assisted microscope camera. The findings were analysed statistically and interpreted in respect of age group, oral site, and sex. Transformation of an angulated and polygonal normal oral squamous cell into a keratinized narrow strip or ribbon-like flat projection results in what is called a keratinized strap cell (KSC). Nuclear pleomorphism in keratinized strap cells was observed to be narrow spindle, rod, and bar-shaped and to resemble Anitschkow cells. From the nature of the staining, the structural peculiarity, and the resemblance to Anitschkow cells, KSC, a rarely observed oral cytological atypia, were renamed as keratinized strap (Anitschkow) (KSC-A) cells. Cytometrically, the nuclear-to-cytoplasmic (N/C) ratio for KSC-A was calculated to be 1:11.2 for males and 1:11.3 for females; these are more than those for the normal counterparts. Rare occurrence, cellular keratinization, nuclear pleomorphism, hyperchromasia, and increased N/C ratios for KSC-A in oral carcinoma, for both sexes, indicate a state of malignancy; this finding is, thus, of practical value for early detection and diagnosis of oral squamous cell carcinoma patients.

Gadadhar Parida

Papers

Pattern of Keratinization in Oral Squamous Cells during Carcinogenesis

Genotoxicity of tobacco and alcohol on human oral mucosal cells

Cytomorphometric analysis of keratinized round cells in human oral carcinoma

An in vivo cytogenetic analysis of human oral squamous cell carcinoma

Keratinized strap cells: a rare cytological atypia resembles Anitschkow cells, in human oral neoplasm