HPV16 genotype, p16/Ki-67 dual staining and koilocytic morphology as potential predictors of the clinical outcome for cervical low-grade squamous intraepithelial lesions.

OBJECTIVE: To evaluate the association of human papillomavirus (HPV) 16 and non-16 genotype, p16/Ki-67 dual staining and koilocytosis and their role in the prediction of the clinical outcome of low-grade squamous intraepithelial lesion (LSIL) cytology. METHODS: One hundred and fifty-five patients with LSIL were followed up and recorded as progression, persistence or regression. HPV genotyping was performed for high-risk HPV (hrHPV) DNA-positive cases. Koilocytosis was reviewed and p16/Ki-67 dual staining was performed on reprocessed conventional cytology slides. RESULTS: HPV16 was the most frequent genotype found in 16.3% of cases. p16/Ki-67 dual staining was positive in 36.1% of all cases. Progression, including concurrent cervical intraepithelial lesion grade 2 or above (CIN2+), was recorded in 13.8% of cases. A statistically significant difference between progressive and non-progressive cases was shown by the following: hrHPV-positive versus hrHPV-negative (P = 0.022), HPV16-positive versus non-16 HPV-positive (P < 0.001) and p16/Ki-67-positive versus p16/Ki-67-negative (P < 0.001) cases. Cases with combined HPV16 and p16/Ki-67 positivity showed the highest progression rate (58.3%). Non-koilocytic HPV16-positive cases showed a 50% progression rate compared with 10.1% for koilocytic non-16 HPV-positive cases (P = 0.010). The sensitivity of p16/Ki-67 dual staining for the detection of CIN2+ lesions was 80%, comparable with hrHPV (85%). The specificity of p16/Ki-67 dual staining was 71% and of hrHPV 42%. The highest specificity was found for HPV16 genotype presence (91%), but with low sensitivity (50%). CONCLUSION: HPV genotyping, p16/Ki-67 dual staining and koilocytic morphology can be useful in the prediction of clinical outcome in women initially diagnosed with LSIL cytology.

Intraoperative cytology of clear cell carcinoma of the ovary.

OBJECTIVE: To describe the cytomorphology of clear cell carcinoma (CCC) of the ovary in intraoperative samples of peritoneal fluid, imprint and scraping samples of the tumour tissue. STUDY DESIGN: Fourteen histologically confirmed cases, stained by standard cytological procedures, were analysed by light microscopy. RESULTS: In 33.3% of peritoneal fluid samples and 92.9% of imprint and scraping cytological samples, besides variable clear cell cellular morphology, one or both distinct cytological characteristics were observed: eosinophilic, hyaline, extracellular, globular substance with or without formation of a 'raspberry' body and an eosinophilic, intracytoplasmic inclusions. These structures were clearly seen only in samples stained by May-Grünwald-Giemsa. CONCLUSION: Using cytological analysis of imprint and scraping samples of ovarian tumours it is possible to make a precise intraoperative cytological diagnosis in most cases of CCC of the ovary.

Morphometry and digital AgNOR analysis in cytological imprints of benign, borderline and malignant serous ovarian tumours.

AIM: The aim of the study was to determine values of a quantitative morphometry analysis of nuclear characteristics and argyrophilic nucleolar organizer regions (AgNORs) in differential cytodiagnosis of benign, atypically proliferating (borderline) and malignant serous ovarian tumours. METHODS: Cytological imprints of benign (n = 20), borderline (n = 19) and malignant (n = 20) ovarian serous tumours were analysed. A computerized, digital analysis was used to determine morphometric nuclear features, the number and characteristics of single AgNORs, cluster AgNORs, total AgNOR and AgNOR area/nucleus (relative area) ratio. According to their size AgNORs were classified in three categories. A one-way variance analysis and post hoc test (Scheffé) were used for statistical analysis. RESULTS: The morphometric nuclear analysis showed that benign, borderline and malignant serous ovarian tumours are statistically different (P < 0.001) according to the area and outline, the values being highest in malignant tumours and lowest in the borderline group. Digital analysis of AgNORs in benign, borderline and malignant groups showed that the total AgNOR number increases with progression of the lesion (meaning tumour malignancy) significantly (P < 0.001) between benign and malignant as well as between borderline and malignant serous ovarian tumours (P < 0.001). The progression of the lesion malignancy was accompanied by a significant (P < 0.001) progressive increase of the total and relative AgNOR area per nucleus. The AgNOR size increases from benign to malignant tumours and a statistically significant difference (P < 0.001) was observed in all three groups regarding small and large AgNORs. CONCLUSION: Combining different markers of morphometric nuclear characteristics and AgNOR values could improve differential cytodiagnosis of benign, borderline and malignant serous ovarian tumours.

Adenoid cystic carcinoma of Bartholin's gland: a case report.

OBJECTIVE: A case of adenoid cystic carcinoma (ACC) of the Bartholin's gland in a 34-year-old woman with unusual presentation and early recurrence is reported. METHODS: Clinical and histologie features were recorded. Immunohistochemical stains and cell-cycle analysis by flow cytometry technique on paraffin-embedded tumor tissue were performed. RESULTS: The tumor presented as a painful nodule in the episiotomy scar three months after delivery. Initial treatment included only wide local excision. Six months later local recurrence occurred despite clear surgical margins. Histologically a predominant "classic" cribriform growth pattern was identified. Immunoreactivity in tumor cells supported dual epithelial-myoepithelial differentiation. Estrogen and progesterone receptors were negative. The DNA histogram revealed a diploid stemline and a low S-phase fraction. CONCLUSION: ACC of the Bartholin's gland is a rare malignant tumor with great propensity for local recurrence. The optimal therapeutic approach has not been established due to the lack of well-defined prognostic parameters.

Chromosomal anomalies in abnormal human pregnancies.

OBJECTIVE: The aim of this study was to describe the cytogenetic observations on abnormal human pregnancies (anembryonic pregnancy, early fetal loss, and hydatidiform moles), and to detect the most frequent or typical chromosomal aberration for anembryonic pregnancy and early fetal loss. STUDY DESIGN: Abnormal pregnancies were divided into three clinical and morphological groups: (a) anembryonic pregnancy; (b) early fetal loss, and (c) hydatidiform mole. Of the 119 karyotyped tissue samples, 42 (35%) were from anembryonic pregnancies, 64 (54%) from early fetal losses, and 13 (11%) were from hydatidiform moles (6 complete and 7 partial moles). Long-term cultures of chorionic villi and GTG-banding techniques were used for chromosome analysis. RESULTS AND CONCLUSION: The overall frequency of chromosome anomalies among the 119 karyotyped spontaneous abortions was found to be 37.8%. Trisomy (double trisomy included) accounted for 35.6% of all aberrations, followed by polyploidy (33.3%), mosaicism (11.1%), structural abnormalities (4.4%), and monosomy X (2.2%). Although the difference was not statistically significant, single trisomy was the predominant chromosome abnormality found in anembryonic pregnancies (64.3 %) while in cases of early fetal loss, trisomy (double trisomy included) (38.9%) and triploidy (27.8%) were quite frequently present. The frequency of triploidy among all chromosomal abnormalities was 28.9%, and 53.8% of them were found in partial hydatidiform mole. The rest of them were almost exclusively found in early fetal losses. Complete hydatidiform moles (androgenetic in origin) were present in 13.3% of all aberrations, of which 83.3% had a 46,XX, and the rest of them had a 46,XY karyotype.

Epidermal growth factor-receptor expression correlates with tumor cell proliferation and prognosis in gastric cancer.

Currently, the most accurate prognostic indicator in gastric cancer is stage. Studies on proliferating cell nuclear antigen (PCNA) in gastric cancer have demonstrated that the PCNA labeling index correlates with depth of invasion, organ metastasis, vascular invasion, and tumor stage, suggesting that this marker may be a valuable prognostic factor. Epidermal growth factor (EGF) promotes the growth of cells of both ectodermal and mesodermal origin, and plays an important role in cellular proliferation and differentiation. Furthermore, there has been increasing evidence that growth factors and their receptors are involved in carcinogenesis. The aim of this study was to investigate the correlation between expression of the EGF-receptor (EGF-r) and proliferative activity (PCNA labeling index) in gastric cancer by immunohistochemical analysis. Our preliminary results on 56 gastric cancers indicate that the PCNA labeling index correlates with EGF-r immunoreactivity. Furthermore, survival was significantly lower in patients with EGF-r positive tumors and a high PCNA labeling index. These in situ observations suggest that EGF-r may play an important role in the growth regulation of human gastric carcinomas.

Transvaginal sonography and hysteroscopy in women with postmenopausal bleeding.

OBJECTIVE: To make a prospective comparison between endometrial thickness determined by transvaginal sonography (TVS) and hysteroscopic findings in women with postmenopausal bleeding with histologic findings obtained by dilatation and curettage (D&C). METHODS: Eighty-one patients who had not received hormonal replacement therapy were scanned by transvaginal probe, and double-layer endometrial thickness was measured 1 day before hysterectomy and D&C. RESULTS: The histologic diagnosis was atrophy in 12 cases, irregular proliferative changes in 21, endometrial polyps in 16 hyperplasia in 16 and endometrial carcinoma in 16. TVS detected 46 of 48 pathologic conditions, including all cases of endometrial carcinoma if the endometrial thickness (both layers) was > or = 5 mm (sensitivity 95.8%, specificity 4.5%). Hysteroscopy also detected the endometrial pathology in 46 of 48 cases but with a higher specificity (sensitivity 95.3%, specificity 93.9%). CONCLUSION: TVS and hysteroscopy are complementary diagnostic methods and could be accurately used to discriminate normal and pathologic conditions in patients with postmenopausal bleeding.

Proliferating cell nuclear antigen (PCNA) as a prognostic factor for colorectal cancer.

PCNA (proliferating cell nuclear antigen) is a cell cycle related protein that is maximally elevated in late G1 and S-phase of proliferating cells. 114 biopsy specimens of colorectal cancer were immunolabeled with PC 10 which specifically recognizes PCNA; Dukes' staging and histological grading were estimated for each case. All patients were followed-up for at least 60 months or to death. All data were analysed by the computer program NCSS (Number Cruncher Statistical System). According to the results, PCNA-index may be considered an independent prognostic factor for colorectal cancer; it may also be helpful in supporting the therapeutic strategies based only on Dukes' stage.