OBJECTIVETo investigate the clinical, pathological and immunohistochemical features of vulvar intraepithelial neoplasia (VIN).

METHODSAccording to the 2004 modified terminology of International Society for the Study of Vulvovaginal Diseases (ISSVD), the cases were diagnosed as VIN from patients who had performed vulvar biopsy in Beijing Wuzhou Women's Hospital from February 2009 to December 2011, which were reclassified as usual VIN and differentiated VIN. The clinical and pathological studies were conducted respectively. MaxVision immunohistochemical staining was used to detect the expression of Ki-67, p16 and p53 proteins.

RESULTSThere were 20 cases of VIN in 237 patients, and the incidence of VIN was 8.4% in all of contemporary vulvar biopsy. In 17 cases of usual VIN, mean age was 29.6 years, the lesion typically presented with atypical cells involving almost all layers of the epithelium, which was equivalent to the high-grade squamous intraepithelial neoplasia of cervix. Immunohistochemistry for Ki-67 and p16 was strongly positive in usual VIN. High risk human papillomavirus (HPV) detection was also positive. The incidence of differentiated VIN was less than usual VIN, and there were only 3 cases in this study. In differentiated VIN, patients aged over 50 years, with mean of 53.7 years, and the lesion most commonly presented with lichen sclerosis background. There were epithelial thickening and extending, and parakeratosis, and atypia was strictly confined to the basal and parabasal layers of the epithelium where the cells enlarged with abundant eosinophilic cytoplasm, presented with prominent nucleoli, increased cellularity and abnormal keratinization. In differentiated VIN, p53 was strongly positive, Ki-67 and p16 immunohistochemical expression was confined to the basal layer only.

CONCLUSIONSVIN is a precursor of invasive squamous cell carcinoma of the vulva. The modified terminology of ISSVD classifies VIN as high-grade lesions. Definitive pathological diagnosis of VIN plays an important role in its timely treatment and the prevention of vulvar carcinoma.

Adult ; Carcinoma in Situ ; metabolism ; pathology ; virology ; Cyclin-Dependent Kinase Inhibitor p16 ; metabolism ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen ; metabolism ; Middle Aged ; Papillomavirus Infections ; pathology ; Tumor Suppressor Protein p53 ; metabolism ; Vulvar Neoplasms ; metabolism ; pathology ; virology ; Young Adult

ObjectiveTriple-negative breast cancer (TNBC) is the breast cancer subtype with the worst prognosis, and lacks effective therapeutic targets. Colony stimulating factors (CSFs) are cytokines that can regulate the production of blood cells and stimulate the growth and development of immune cells, playing an important role in the malignant progression of TNBC. This article aims to construct a novel prognostic model based on the expression of colony stimulating factors-related genes (CRGs), and analyze the sensitivity of TNBC patients to immunotherapy and drug therapy. MethodsWe downloaded CRGs from public databases and screened for differentially expressed CRGs between normal and TNBC tissues in the TCGA-BRCA database. Through LASSO Cox regression analysis, we constructed a prognostic model and stratified TNBC patients into high-risk and low-risk groups based on the colony stimulating factors-related genes risk score (CRRS). We further analyzed the correlation between CRRS and patient prognosis, clinical features, tumor microenvironment (TME) in both high-risk and low-risk groups, and evaluated the relationship between CRRS and sensitivity to immunotherapy and drug therapy. ResultsWe identified 842 differentially expressed CRGs in breast cancer tissues of TNBC patients and selected 13 CRGs for constructing the prognostic model. Kaplan-Meier survival curves, time-dependent receiver operating characteristic curves, and other analyses confirmed that TNBC patients with high CRRS had shorter overall survival, and the predictive ability of CRRS prognostic model was further validated using the GEO dataset. Nomogram combining clinical features confirmed that CRRS was an independent factor for the prognosis of TNBC patients. Moreover, patients in the high-risk group had lower levels of immune infiltration in the TME and were sensitive to chemotherapeutic drugs such as 5-fluorouracil, ipatasertib, and paclitaxel. ConclusionWe have developed a CRRS-based prognostic model composed of 13 differentially expressed CRGs, which may serve as a useful tool for predicting the prognosis of TNBC patients and guiding clinical treatment. Moreover, the key genes within this model may represent potential molecular targets for future therapies of TNBC.