Value of HPV-DNA test in women with cytological diagnosis of atypical glandular cells (AGC).

OBJECTIVE: This study analyzed whether HPV (human papillomavirus) testing contributes towards defining histological abnormalities in women with atypical glandular cells (AGC) diagnosed at cervical cytology. STUDY DESIGN: One hundred and eight women with conventional cervical cancer screening smears suggestive of AGC not otherwise specified (AGC-NOS) and favor neoplastic (AGC-FN) were consecutively enrolled. All women underwent colposcopic examinations and biopsy was performed according to the cytopathologic and/or colposcopic abnormalities present. All specimens were tested for high risk HPV genotypes by Roche's polymerase chain reaction reverse line blot assay. The chi-square test was used to evaluate the association between HPV findings and a diagnosis of high-grade pre-invasive or invasive disease (CIN 2 or worse) taking negative tests or CIN 1 as a reference. Odds ratios (OR) with their respective 95% confidence intervals (95%CI) were used to evaluate the magnitude of the association between HPV testing and CIN 2 or worse. Sensitivity, specificity and their respective 95% confidence intervals (95%CI), positive predictive values (PPV) and negative predictive values (NPV) were also calculated. RESULTS: Final diagnosis revealed a negative outcome in 80 cases (74%), cervical epithelial neoplasia 1 (CIN 1) in 13 cases (12%), CIN 2 or worse in 12 cases (11%) and glandular neoplasia in 3 (3%) cases. The overall detection rate of HPV was 21% (23/108). Neoplasia was significantly associated with positive HPV-DNA in women with AGC-NOS (OR=15.21; 95%CI: 2.64-87.50); however, there was no significant association between a histological diagnosis of neoplasia and HPV positivity in women with AGC-FN (OR=3.00; 95%CI: 0.36-24.92). The sensitivity, specificity, positive predictive value and negative predictive value of HPV-DNA testing for the detection of CIN 2 or worse in women with AGC-NOS were 71%, 86%, 29% and 97%, respectively. In women with AGC-FN, these values were 50%, 75%, 66% and 60%, respectively. CONCLUSIONS: HPV testing at the time of colposcopy for patients with AGC in whom no colposcopic abnormality is found may be a powerful ancillary tool for identifying women at a high risk of underlying significant cervical lesions.

Endometrial polyp with sex cord-like pattern.

We report on an unusual endometrial polyp in a postmenopausal woman taking tamoxifen for 7 years after surgical resection of a breast carcinoma. A 63-year-old woman with endometrial thickening was submitted to hysteroscopy with biopsy, which revealed a polyp with a sex cord-like pattern. The hysterectomy specimen showed florid adenomyosis, and in the background, there were rare sex cord-like foci. Immunohistochemistry can be useful in differentiating sex cord-like elements from metastatic breast cancer to endometrium. This is, to our knowledge, the first observation in literature correlated to tamoxifen intake.

Expression of cyclooxygenase-2 (COX-2) and Ki67 as related to disease severity and HPV detection in squamous lesions of the cervix.

OBJECTIVES: To assess the expression of cyclooxygenase (COX-2) and Ki67 in cervical squamous lesions in relation to disease severity and human papillomavirus (HPV) detection. SUBJECTS AND METHODS: For this cross-sectional study, 223 women subjected to diathermic conization of the cervix have been enrolled, between February 2001 and April 2004. All patients undertook pelvic examination, including colposcopy and collection of samples for Hybrid Capture II (HCII). Pathological assessment disclosed: 9 cases of normal epithelium/cervicitis, 33 CIN1, 28 CIN2, 146 CIN3 and 7 invasive squamous cell carcinomas. COX-2 and Ki67 protein expression was determined with immunohistochemistry. COX-2 immunoreactivity grading was based on the German ImmonoReactive score. The continuum percentage of positive cells was used for the assessment of nuclear Ki67 expression. RESULTS: Expression of COX-2 did not correlate with disease severity and with Ki67 expression. The HPV detection rates did not differ significantly across COX-2 protein expression strata, ranging from negative to strong expression. Ki67 expression, however, was higher in the CIN3 group (P = 0.001) as compared to the specimens rendered as normal/cervicitis. CONCLUSIONS: COX-2 protein expression did not correlate with disease severity or Ki67 expression.

Human papillomavirus DNA detection and histological findings in women referred for atypical glandular cells or adenocarcinoma in situ in their Pap smears.

OBJECTIVE: To evaluate the association between high-risk human papillomavirus (HPV) DNA detection and histological diagnosis in women referred for atypical glandular cells (AGC) or adenocarcinoma in situ (AIS) at Pap smear. METHODS: In this cross-sectional study, 146 women referred for AGC (124), AGC with high-grade squamous intraepithelial lesion (HSIL) (15), or AIS (7) were tested for HPV DNA using Hybrid Capture II (HC II). All women underwent colposcopic examination, and cervical biopsy was performed for 95 patients. Fifty-one women referred due to AGC with normal colposcopy and normal second Pap smear were scheduled for control visits every 4 months. RESULTS: The overall prevalence of HPV DNA was 38%. HPV DNA was detected in 93% of the women with HSIL associated with AGC and in 71% of women with AIS Pap smear, being significantly higher when compared with the prevalence (29%) in women with AGC alone. Forty-five women (30.8%) had clinically significant histological lesions (CIN 2 or worse). High-risk HPV DNA was detected in only 16% of the women without significant abnormalities in biopsy, in contrast to 96% of those who had CIN 2 or CIN 3 and 75% of women with AIS. Eighty-five percent of women with invasive cervical carcinoma (squamous or adenocarcinoma) tested positive for HPV DNA. HPV DNA detection was significantly associated with histological diagnosis of CIN 2 or worse, with an odds ratio (OR) = 51.8 (95% CI 14.3-199.9). CONCLUSION: HPV DNA detection was strongly associated with the severity of cervical lesion (CIN 2 or worse) in women referred for AGC or AIS in their Pap smear. These data implicate the use of HPV testing in triage of women with AGC Pap smears.

Immunohistochemical patterns for alpha- and beta-catenin, E- and N-cadherin expression in ovarian epithelial tumors.

OBJECTIVES: This study aims were to analyze and compare the E- and N-cadherin, beta- and alpha-catenin expression in benign and malignant epithelial neoplasms of the ovary, correlating with tumor staging, histological grade, and presence of metastases during evolution. METHODS: Immunohistochemical reactions were performed on paraffin-embedded tissues and evaluated according to the number of positive, stained cellular structures and reaction intensity for each molecule. Information about histological type and grade, tumoral stage, and disease evolution was obtained from the patients' clinical records. RESULTS: Most of the carcinomas showed more intense beta-catenin reaction (P = 0.02). More than 50% of the endometrioid carcinomas showed increased beta-catenin expression, with a large number of positive cells and more intense staining, being the same also observed for most of the serous benign tumors (P < 0.01). E-cadherin membrane expression was frequently observed in carcinomas without metastasis, whereas cases with metastases in evolution were negative or showing E-cadherin expression only in the cytoplasm (P = 0.04). N-cadherin expression differed according to histological type and grade and alpha-catenin was also related to histological type, but these findings were not conclusive. CONCLUSIONS: Increased beta-catenin expression was more frequent in ovarian carcinomas, especially, but not only, in the endometrioid ones. The maintenance of E-cadherin expression in cellular membrane may be an independent marker of good prognosis in ovarian cancer. New studies about N-cadherin and alpha-catenin and their importance during ovarian carcinogenesis will be required.

p53, estrogen and progesterone receptors in diagnostic curettage for endometrial adenocarcinoma and their correlation with morphological data and disease stage at hysterectomy.

CONTEXT: Diagnostic staging is an important prognostic factor for endometrial adenocarcinoma. Apart from the histological type and histological grade, some markers seem to be associated with the stage and biological behavior of the disease. Among these are p53, estrogen and progesterone receptors. OBJECTIVE: The objectives of the present study were: to compare histological type and grading of endometrial carcinoma in curettage and hysterectomy samples; to assess expression of p53, estrogen and progesterone receptors in curettage specimens; and to correlate these data with morphology and staging of the disease in hysterectomy specimens. TYPE OF STUDY: Retrospective. SETTING: Department of Pathology, Faculdade de Ciências Médicas, Universidade Estadual de Campinas. SAMPLE: Histological diagnosis from 51 consecutive files. PROCEDURES: Immunohistochemical reactions for p53, estrogen and progesterone receptors via the avidin-biotin-peroxidase method in 51 curettage samples endometrial carcinoma were compared with the morphological data and disease stage in hysterectomy. Marker expression was correlated with histological type and grade and the final stage of the disease. RESULTS: According to the histological type: 44 cases (86%) were of endometrioid and 7 (14%) non-endometrioid carcinoma. p53 expression was observed in 16% of endometrioid and 71% of non-endometrioid cases (p<0.05). Although estrogen expression was more evident in endometrioid (54%) than non-endometrioid cases (29%), this was not statistically significant. Progesterone receptor expression was significantly higher in endometrioid than non-endometrioid cases (70% vs. 14%, p<0.05). According to the histological grade: Estrogen and progesterone receptors were expressed more frequently in grade I endometrioid carcinoma, while p53 was mainly reported in tumor grades II and III. According to final disease stage: p53 and estrogen expression in curettage specimens was not related to stage; progesterone receptors, however, were expressed significantly less in advanced disease. CONCLUSION: p53 was observed in the majority of non-endometrioid and in high-grade endometrioid carcinoma, but was not related to stage. Estrogen and progesterone receptors were mainly found in grade I endometrioid carcinoma. The markers studied in curettage were no more valuable for predicting the disease stage than classical histological criteria.