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The aim of the study is to evaluate and correlate the morphology and cell density of epithelial cells adhering to lens capsule surgically removed from the anterior central region with lens clarity and type of cataract present in patients with or without type 2 diabetes. Capsulorhexis specimens were obtained from patients who had undergone phacoemulsification cataract surgery. All the samples were centrifuged and stained by the aid of Papanicolaou technique and were observed under light microscope. We determinated the mean cell density, the degree of epithelial damage, and morphological indicators of cells such as cell area and the nucleus–plasma ratio. Patients with cataract demonstrated a statistical significant decrease in cell density and an heterogeneous cell picture in which enlarged cells dominated. In addition, type 2 diabetics with cataract had a significantly even lower mean epithelial cell density by the presence of larger cell area with smaller nucleus–plasma ratio. More pronounced alterations in the lens epithelium were correlated not only with the presence of cortical cataract, increased fasting blood sugar, and increased HbA1c but also with the prolonged duration of diabetes and the co-existence of diabetic retinopathy. It seems that density and morphology of the anterior lens epithelial cells determine the lens epithelium damage which is more profound in hyperglycemia and in cortical cataracts. The changes in lens epithelium seem to play an important role in cataractogenesis. © 2015, Springer Science+Business Media Dordrecht.

This report of the Editorial Advisory Board of Cytopathology gives the results of a survey of medical practitioners in cytopathology, which aimed to find out their views on the current situation in undergraduate and postgraduate training in their institutions and countries. The results show that training in cytopathology and histopathology are largely carried out at postgraduate level and tend to be organized nationally rather than locally. Histopathology was regarded as essential for training in cytopathology by 89.5% of respondents and was mandatory according to 83.1%. Mandatory cytopathology sections of histopathology were reported by 67.3% and specific examinations in cytopathology by 55.4%. The main deficiencies in training were due to its variability; there were insufficient numbers of pathologists interested in cytology and a consequent lack of training to a high level of competence. Pathologists without specific training in cytopathology signed out cytology reports according to 54.7% of responses, more often in centres where training was 3-6 months or less duration. Although 92.2% of respondents thought that specialist cytology should not be reported by pathologists without experience in general cytopathology, that practice was reported by 30.9%, more often in centres with small workloads. The survey report recommends that 6-12 months should be dedicated to cytopathology during histopathology training, with optional additional training for those wanting to carry out independent practice in cytopathology. Formal accreditation should be mandatory for independent practice in cytopathology. When necessary, temporary placements to centres of good practice should be available for trainees intending to practise independently in cytopathology. There should be adequate numbers of pathologists trained in cytopathology to a high level of competence; some of their time could be released by training cytotechnologists and trainee pathologists to prescreen cytology slides and assess adequacy of fine-needle aspiration samples when immediate diagnosis was not required. The survey demonstrated a clear need for European and international guidelines for training in cytopathology.

Journal URL: http://www.iiar-anticancer.org/main.php?id=2

Journal URL: http://www.iiar-anticancer.org/main.php?id=2

Objective: The aim of the present study was to evaluate the expression of pan-cadherin and β-catenin in cervical smears with various types of infectious agents. Patients and Methods: Cervical smears obtained from 53 women, aged 21-65 years, with a diagnosis of specific inflammation were examined in our study. Eighteen subjects were infected by Candida albicans, 18 by Gardnerella vaginalis, nine by Bacteroides spp. and eight by Chlamydia trachomatis. All infectious agents found in the smears were at the same time confirmed by the microbiological laboratory methods. We performed a biotin-streptavidin-peroxidase immunocytochemical method using anti-β-catenin (Clone 12F7) and anti-pan-cadherin (pan, polyclonal) antibodies. Results: Aberrant expression of pan-cadherin was found in the cytoplasmic membrane of glandular, metaplastic, superficial and intermediate squamous cells in all types of infections. With regard to β-catenin, this was expressed in majority (90%) of glandular and metaplastic cells in all types of infections and in a small proportion (15%) of superficial and intermediate squamous cells in infections caused by C. albicans and G. vaginalis. Conclusion: Our data show that infectious agents may cause alterations in the expression and distribution of these adhesive molecules, which can be recognized in cervical smears. Additional studies in larger sets of patients should help clarify this issue further. © 2007 The Authors.

Aim: Epithelial cadherin (E-cadherin), a transmembrane glycoprotein involved in calcium-dependent homophilic cell-cell adhesion, is expressed aberrantly during cervical carcinogenesis. E-cadherin expression and putatively implicated predictors in healthy women remain a rather under-investigated area. The objective of this study is to evaluate the possible associations between E-cadherin expression and reproductive/lifestyle factors in cervical epithelial cells from postmenopausal women. Methods: A total of 105 healthy postmenopausal women (aged 45-68 years old) attending a university menopause clinic were enrolled in this cross-sectional study. Pap smears were derived and E-cadherin immunostaining was evaluated in squamous, glandular and squamous metaplastic cells, using a semi-quantitative method (rating scale: 0-3). Reproductive and lifestyle factors were obtained from patients' chart review. Results: In squamous cells, women with a history of 0-1 deliveries presented with a higher score vs women with 2-4 deliveries (P = 0.003). Social drinkers and women drinking alcohol daily exhibited a higher E-cadherin immunostaining score in squamous cells vs non-drinkers (0.96 ± 0.72 vs 0.56 ± 0.65, P = 0.004). A higher dietary calcium intake was marginally correlated with a lower staining score in squamous cells (0.94 ± 0.78 for low, 0.71 ± 0.70 for average, 0.45 ± 0.52 for high consumption, P = 0.073). Conclusions: E-cadherin expression seems to be associated with reproductive history and lifestyle habits in squamous cervical cells from healthy postmenopausal women. E-cadherin might participate in the molecular mechanisms underlying the role of parity as a risk factor for cervical cancer. © 2008 Japan Society of Obstetrics and Gynecology.

Objective: To evaluate proliferating cell nuclear antigen (PCNA) and epidermal growth factor receptor (EGFR) expression in urine ThinPrep (TP) specimens, to compare these findings with clinical and histological features and to determine whether these immunomarkers are predictive of clinical stage. Patients and Methods: The TP processed urine samples and the corresponding tissue sections from 42 patients with newly diagnosed bladder cancer (18 non-muscle invasive and 24 muscle invasive) were included in our study. Urine was collected for cytological evaluation before transurethral resection. Tumour grade and clinical stage were assessed from the transurethral resection specimens. The EGFR and PCNA expression was obtained by an automated immunostainer. Results: There was a remarkable concordance in the expression of both antibodies in TP smears and tissue sections. No significant association was detected for any of the immunomarkers examined with regard to tumour grade. The EGFR expression as well as grade of malignancy were significantly associated with stage of disease (P = 0.0001). PCNA was not found to be a significant predictor of stage (P = 0.210). Conclusion: Our data suggest that the evaluation of grade of malignancy and EGFR immunopositivity can be considered as reliable predictors of disease stage in urine TP specimens.

In contrast to the conventional notion regarding tumour development as a cell autonomous process in which the major participants were the cancer cells, increasing evidence attributes important role in the stromal components, namely fibroblasts, and view the tumour as a heterogenous mixture of different cell types. These different types of cells, being cancer cells, fibroblasts, endothelial cells, and others, interact reciprocally and play an almost equally important role in the manifestation of certain aspects of the malignant phenotype. The elucidation of the mechanistic base of such interactions, besides the contribution to understand fundamental aspects of tumour cell biology, promises important applications in diagnosis, prognosis and therapy of the disease.

Objective: GHRH is secreted by the hypothalamus and, upon binding to specific GHRH receptors in the pituitary, stimulates growth hormone (GH) production and release from the pituitary. In addition to this neuroendocrine action, accumulated evidence implies additional roles for GHRH in carcinogenesis in non-pituitary tissues. In vitro and in vivo studies have shown that splice variant 1 (SV1) of the GHRH receptor, which is widely expressed in non-pituitary tissues and cancers, can mediate the proliferative effects of GHRH. The aim of the present study was to investigate the operation of an autocrine stimulatory loop between GHRH and SV1 in primary breast tumors. Design: Fifty-three primary breast tumors were evaluated for GHRH and SV1 expression. Methods: Expression of GHRH and SV1 was assessed by immunohistochemistry using anti-GHRH SV95 and anti-SV1 2317/5 polyclonal antibodies. Results: About 40% of the specimens tested express GHRH and/or SV1 (approx. 25% each), while in 35% of these positive specimens co-exprcssion of these antigens was detected (P < 0.01). Furthermore, a correlation of GHRH, but not SV1, expression was detected in lobular compared with ductal carcinomas. Conclusions: These results constitute the first demonstration for the expression of GHRH and SV1 in primary breast cancers, and provide evidence for the operation of an autocrine stimulatory loop between GHRH and SV1 in primary cancers. Our findings indicate that GHRH analogs could have diagnostic and therapeutic applications for the management of breast cancer.

Existing evidence indicates that, in addition to its neuroendocrine action, growth hormone-releasing hormone (GHRH) acts directly on several nonpituitary tissues, especially neoplasms, and stimulates cell proliferation. We have recently reported that a splice variant of the receptor (SV1) is expressed in various normal tissues and particularly in tumor tissues, producing mitogenic effects on GHRH binding. By using HEC-1A human endometrial carcinoma cells, which express endogenous SV1, we show that, in addition to its ability to mediate the mitogenic effects of GHRH, SV1 also possesses relatively high intrinsic, ligand-independent activity. By using an antisense RNA-based approach we found that SV1 ablation reduces the efficacy of colony formation and the rate of cell proliferation of HEC-1A cells in the absence of exogenous GHRH, and decreases their sensitivity to GHRH when the neurohormone is added to the culture media. This ligand-independent stimulation of cell proliferation appears to be a characteristic property of the truncated form of the receptor, because the expression of SV1 and not of the full-length GHRH receptor stimulated the proliferation of 3T3 fibroblasts in the absence of exogenous GHRH, whereas both forms mediated the proliferative effects of GHRH. Evaluation of 21 specimens of human primary endometrial carcinoma for expression of SV1 by immunohistochemistry indicated that in contrast to the GHRH receptor, which is absent, SV1 is expressed in ≈43% of the specimens. These findings indicate that SV1 can operate in a ligand-independent as well as a ligand-dependent manner. The overexpression of this form of GHRH receptor may be associated with carcinogenesis.

Objective: The pathological distinction between parathyroid neoplasms and hyperplasias remains difficult. Changes in cell cycle control may lead to clonal proliferation and precede tumorigenesis. The parathyroid adenoma 1 oncogene, subsequently identified as the gene encoding cyclin D1, has been shown to be important to parathyroid tumour development. In addition to cell proliferation, the mechanisms of parathyroid cell turnover include apoptosis. The tumour-suppressor activity of the fragile histidine triad gene (FHIT) is linked to its proapoptotic function and cell cycle control. We attempted to evaluate the cellular proliferative kinetics and apoptotic function of the parathyroid glands in patients with non-familial hyperparathyroidism (HPT). Design: Tissue specimens were taken from 40 patients with primary HPT (17 adenomas, two carcinomas and 21 primary hyperplasias) and from 30 patients with secondary HPT. Normal glands served as controls. Methods: In a standard immunohistochemical procedure, monoclonal antibodies to Ki-67 antigen and single-stranded DNA were applied to detect cycling and apoptotic cells respectively; polyclonal antibodies to cyclin D1 and Fhit protein were used. Immunostaining was estimated by image analysis and statistical analysis was subsequently performed. Results: Significantly higher proliferative and apoptotic indexes were detected in the diseased glands in comparison with normal controls. In neoplastic and secondarily hyperplastic glands, apoptotic indexes were higher than in primarily hyperplastic glands; the difference between neoplastic and primarily hyperplastic glands was statistically significant (P = 0.034). Cyclin D1 was overexpressed in a considerable proportion of tumours (68.4%). A reduction of Fhit protein immunoreactivity was selectively noticed in carcinomas. Conclusions: In primary hyperplasia, the remarkable proliferation of parathyroid glands may be due to the reduction of the apoptotic process. FHIT gene abnormalities are worthy of investigation in parathyroid carcinogenesis.

Objective: The family of fibroblast growth factors stimulates proliferation of cells of mesenchymal, epithelial and neuroectodermal origin. One of the members of this family, the product of proto-oncogene int-2, fibroblast growth factor-3, has been found to stimulate mitosis of parathyroid cells in culture. Primary and secondary hyperparathyroidism have no clear differences with regard to the histopathological features of the diseased parathyroid glands. Design: This study was undertaken in order to determine whether int-2 protein is immunohistochemically expressed in normal and abnormal parathyroid glands and to investigate whether there is a differential expression of the int-2 gene product between primary and secondary parathyroid disease. Methods: A sheep anti-human int-2 antibody was applied to tissue sections from 3 7 samples of primary parathyroid disease (12 sporadic adenomas, 25 hyperplastic glands), from 30 samples of renal hyperparathyroidism, and from seven normal controls. Int-2 immunostaining was evaluated semi-quantitatively. Results: None of the normal parathyroid glands stained positively. Int-2 immunopositive expression was more frequently detected in specimens of uraemic patients than in those of patients with primary parathyroid growth processes (P = 0.029). The reason for this differential expression appears to be the higher proportion of oxyphilic cells growing in hyperplastic glands of patients with secondary hyperparathyroidism; the latter cells were specifically found to be int-2 immunoreactive. Conclusion: The int-2 gene product is likely to participate in the proliferation of this parathyroid cell subpopulation.

Background: Hypothalamic GH-releasing hormone (GHRH) regulates GH release from the pituitary, but an ectopic production of GHRH has been detected in various non-hypothalamic tissues, especially cancers. Objective: To investigate whether endometrial tumors produce GHRH. Methods: Twenty-four endometrioid, three serous papillary (SP), three mixed type endometrioid/serous papillary adenocarcinomas and one malignant mixed Milllerian tumor (MMMT) were assessed for GHRH inummoreactivity by the polyclonal anti-rabbit antibody SV95 and for the expression of GHRH mRNA by in situ hybridization using an oligonucleotide probe. Results: Increased GHRH immunoreactivity was detected in 15 out of 24 (63%) of the endometrioid tumors, including two out of three (66%) of the mixed type endometrioid/scrous adenocarcinomas but not in the three SP or the MMMT tumor. Cytoplasmic staining was detected in all positive cases, while in three of them strong nuclear localization of GHRH was also revealed. In situ hybridization indicated the presence of GHRH mRNA in six cases, all characterized as positive for GHRH inummoreactivity. Conclusion: GHRH is expressed in a subset of endometrial tumors, of the endometrioid type in particular. A paracrine/autocrine role for GHRH in the development of the disease should be considered.

Objective Classification of hepatic tumours and tumourlike conditions can sometimes be difficult to establish by light microscopy, Our aim was to determine the value of computerized interactive nuclear morphometry in the preoperative prediction of primary or metastatic malignancy as opposed to non-malignant lesions, in fine-needle aspirates (FNA) of hepatic lesions. Methods Alcohol-fixed, Papanicolaou-stained FNA smears of 99 histologically proven hepatocellular carcinomas (HCCs), metastatic neoplasms and benign lesions were measured by computerized image analysis with regard to nuclear major axis, minor axis, perimeter, area, shape factor and hyperchromasia. Data were coded, entered into a computerized database, and statistically analysed with SPSS programs. Results Tukey HSD test for multiple comparisons, assessed for all features except hyperchromasia, showed that the mean values of morphometric features of nonmalignant cells were significantly different from those of malignant cells, either primary or metastatic, whereas differences between morphometric characteristics of HCCs and metastatic neoplasms were insignificant Kruskal-Wallis analysis of variance revealed that hyperchromasia varied among the three groups of samples proportionally to the other nuclear features. The mean differences of all evaluated nuclear variables except minor axis were significant between grades II & III and grade IV HCCs. Morphometric mean values of well-differentiated HCCs differed significantly in comparison with those of non-malignant lesions; however, some degree of overlap was observed in the ranges of minor axis and hyperchromasia mean values. Conclusions The three most important cytological criteria of nuclear malignancy (hyperchromasia, enlargement and anisonucleosis), when quantified by morphometry, may be helpful in the differential diagnosis between noncancerous liver lesions and HCCs (even those of high differentiation), since all the morphometric data showed pronounced differences between malignant and benign groups. Morphometry may also be used as a complementary tool in the cytological grading of HCCs. (C) 2000 Lippincott Williams & Wilkins.

The histological similarities of seborrhoeic keratoses and common warts led to the investigation of the possible occurrence of human papillomavirus DNA (HPV-DNA) in a large number of nongenital seborrhoeic keratoses using the in situ hybridization technique, All specimens derived from normal skin (n = 173) were negative for the applied HPV-DNA probe, whereas the HPV genome was detected in 33 of 173 seborrhoeic keratosis specimens (19.65%). Of 34 HPV-positive specimens, 15 contained types 6/11 and 14 types 31/33/35, and 5 showed no positive reaction to the applied types. These results suggest that a considerable percentage of nongenital seborrhoeic keratoses may be related to an HPV infection.

We have examined the distribution of ras p21 oncoprotein expression in cytologic specimens from 73 primary bronchial carcinomas using an immunocytochemical analysis. The cytologic preparations studied represent the two major groups of histological types of lung cancer: Small Cell Lung Carcinoma (SCLC) and Non-Small Cell Lung Carcinoma (NSCLC) (squamous cell carcinoma and adenocarcinoma). The differential expression of ras p21 oncoprotein correlated with histological classification and was found in 30% of 23 small cell lesions, 61% of 28 squamous cell lung carcinomas and 32% of 22 adenocarcinomas. The ras p21 oncoprotein was commonly expressed in NSCLC cases (48%) as compared to SCLC cases (30%).

This study was undertaken to determine the expression of p53 gene in cytologic specimens from benign and malignant breast lesions. To detect p53 an immunocytochemical assay with p53 (pAb421) monoclonal antibody was used. Abnormalities in p53 expression were found in 19 out of 40 Fine Needle Aspiration (FNA) smears with infiltrating ductal breast carcinomas. Benign epithelial breast cells obtained from fibroadenomas, fibrocystic disease and smears from nipple discharge reacted negatively for p53 in 38 out of 39 cases. Moderate positive reaction, confined to a few clusters of epithelial cells, was observed in one smear of fibroadenoma with cellularity. The results recorded in this study show that no significant association was found between p53 staining and stage of disease, tumor size or nodal status and that the immunocytochemical assay represents a simple method for the detection of p53 associated proteins in breast lesions.