The utility of immunohistochemistry in the differential diagnosis of gynecologic disorders.

CONTEXT: Immunohistochemistry has assumed an increasing role in the identification and characterization of gynecologic disorders including lesions with deceptively bland morphology, uncommon and underdiagnosed neoplasms, and neoplasms with specific genetic alterations associated with overexpression or loss of expression of specific proteins. The diagnostic accuracy has been significantly improved owing to the discovery and increasing experience with the tumor-associated biomarkers, and the increasing demand for precise tumor classification to assess suitability for the expanding therapeutic modalities including clinical trials. OBJECTIVE: To differentiate lesions of the gynecologic tract through the use of effective immunohistochemical panels. DATA SOURCES: Literature review and authors' personal practice experience. CONCLUSIONS: The application of diagnostic and prognostic immunohistochemical panels has enabled pathologists to better guide therapeutic decisions and to better predict the clinical outcome. It is now well established that the use of ancillary testing, including immunohistochemistry, has a significant power in the identification, differentiation, and classification of reactive, premalignant, and malignant gynecologic disorders. This article discusses the utilities and pitfalls of the commonly used immunohistochemical markers in the context of overlapping morphologic features encountered in the uterus, ovaries, and fallopian tubes.

Yes-associated protein (YAP) modulates oncogenic features and radiation sensitivity in endometrial cancer.

BACKGROUND: Yes-associated protein (YAP) is a transcriptional co-activator and regulates cell proliferation and apoptosis. We investigated the clinical and biological significance of YAP in endometrial cancer (EMCA). METHODS: YAP expression in 150 primary tumor tissues from patients with EMCA was evaluated by immunohistochemistry and its association with clinicopathological data was assessed. The biological functions of YAP were determined in EMCA cell lines through knockdown/overexpression of YAP. The role of YAP in modulating radiation sensitivity was also investigated in EMCA cells. RESULTS: Increased nuclear YAP expression was significantly associated with higher grade, stage, lympho-vascular space invasion, postoperative recurrence/metastasis and overall survival in estrogen mediated EMCA, called type 1 cancer (p = 0.019,  = 0.028,  = 0.0008,  = 0.046 and  = 0.015, respectively). In multivariate analysis, nuclear YAP expression was confirmed as an independent prognostic factor for overall survival in type 1 EMCA. YAP knockdown by siRNA resulted in a significant decrease in cell proliferation (p<0.05), anchorage-dependent growth (p = 0.015) and migration/invasion (p<0.05), and a significant increase in the number of cells in G0/G1 phase (p = 0.002). Conversely, YAP overexpression promoted cell proliferation. Clonogenic assay demonstrated enhanced radiosensitivity by approximately 36% in YAP inhibited cells. CONCLUSIONS: Since YAP functions as a transcriptional co-activator, its differential localization in the nucleus of cancer cells and subsequent impact on cell proliferation could have important consequences with respect to its role as an oncogene in EMCA. Nuclear YAP expression could be useful as a prognostic indicator or therapeutic target and predict radiation sensitivity in patients with EMCA.

Prevalence of reproductive tract infections, genital prolapse, and obesity in a rural community in Lebanon.

OBJECTIVE: To determine the prevalence of reproduction-related illnesses in a rural community in Lebanon. METHODS: Data were collected through interviews with women in their homes, physical examinations and history taking by physicians in a clinic in the community, and laboratory tests. A total of 557 ever-married women aged 15-60 years were selected randomly. FINDINGS: Just over half of the sample (268, 50.6%) had five or more children, and (320, 78.9%) of women aged < 45 years were using contraception. The prevalence of reproductive tract infections was very low: six (1.2%) women had sexually transmitted diseases and 47 (9.3%) had endogenous reproductive tract infections. None had chlamydial infection or a positive serological finding of syphilis. None had invasive cervical cancer, and only one had cervical dysplasia. In contrast, genital prolapse and gynaecological morbidity were elevated. Half of the women studied (251, 49.6%) had genital prolapse, and 153 (30.2%) were obese. CONCLUSION: The prevalence of reproductive tract infections in this conservative rural community in east Lebanon was low. Possible explanations include the conservative nature of the community, the high rate of utilization of health care services, and the liberal use of antibiotics without a prescription. More importantly, the study showed an unexpectedly high prevalence of genital prolapse and obesity--a finding that has clear implications for primary health care priorities in such rural communities.