In squamous cell carcinoma of the vulva, overexpression of p53 is a late event and neither p53 nor mdm2 expression is a useful marker to predict lymph node metastases.

To offer more tailored treatment to individual patients with squamous cell carcinoma of the vulva, more accurate prediction of lymph node metastases is required. As p53 and mdm2 are genes known to be involved in the development of other tumours, we studied expression of p53 and mdm2 in carcinogenesis of squamous cell carcinoma of the vulva and their clinical relevance. Archival material of 141 T1 and T2 vulvar tumours were used. Of the 141 primary tumours, the corresponding 39 lymph node metastases (LNM) were studied, and in 90 cases the pre-existent epithelia adjacent to the tumour (EAT) and in 14 cases vulvar intraepithelial neoplasia adjacent to the tumour (VIN) was also investigated. Detection of p53 and mdm2 protein was immunohistochemically performed. Scoring categories were: negative (1); weakly positive (2); moderately to markedly positive (3); and markedly positive (4). Overexpression of p53 was seen in 56% of the LNM, 39% of the primary tumours, 21% of the VIN lesions and 0% in the group of EAT. No relation was found between overexpression of p53 in the primary tumour and LNM. Expression of mdm2 was seen in 14% of the primary tumours, of which four cases were marked positive. In the group of LNM no mdm2-positive staining was observed. In the group of EAT, 25% was mdm2-positive, of which six cases were marked positive. In the group of VIN, 36% showed moderate (score 3) mdm2 expression. No relation was found between expression of mdm2 and LNM. In squamous cell carcinoma, overexpression of p53 is a late event in carcinogenesis. Marked expression of mdm2 is rarely seen in vulvar carcinomas, indicating that aberrant p53 cannot induce mdm2 expression. LNM cannot be predicted by detection of these proteins.

Quantitation of proliferation-associated markers Ag-NOR and Ki-67 does not contribute to the prediction of lymph node metastases in squamous cell carcinoma of the vulva.

A key prognostic parameter for vulvar carcinoma is the presence of lymph node metastases. Determination of proliferation markers has been suggested as a method to predict lymph node metastases in several tumor types. If this were true in vulvar carcinomas, reduced surgical therapy for patients with low-risk vulvar carcinoma could be considered. The authors analyzed whether the proliferation-associated markers silver nucleolar organizer region (Ag-NOR) and Ki-67 are predictors for inguinofemoral lymph node metastases in women with vulvar carcinoma. The authors also analyzed whether these proliferation markers are interrelated. Data were obtained from samples of 145 patients with T1/T2 squamous cell carcinoma of the vulva who were treated with vulvectomy and bilateral lymphadenectomy. None of these patients received preoperative therapy, and the invasion depth of the tumors was more than 1 mm. The median age was 71 years. The group consisted of 67 patients with differentiation grade 1, 64 with grade 2, and 18 with grade 3; 22% (15 of 67) of the patients with grade 1, 45% (29 of 64) with grade 2, and 43% (six of 14) with grade 3 had lymph node metastases. Formalin-fixed, paraffin-embedded sections were stained for proliferation markers Ag-NOR and MIB-1 (an equivalent of Ki-67 for fixed material). Both parameters were scored at the tumor stroma interface. Ag-NOR number and areas were quantified by interactive image analysis and Ki-67 index was scored microscopically with a grid. No relation was found between Ki-67 or Ag-NOR and lymph node metastases. A relation was found between Ki-67 and mitotic index (MI), but not between Ag-NOR and MI or Ki-67 index. Therefore, it is questionable whether Ag-NOR is, indeed, a marker for proliferation. The authors conclude that quantitation of Ki-67 and Ag-NOR does not contribute to the prediction of inguinofemoral lymph node metastases in squamous cell carcinoma of the vulva.

The importance of the groin node status for the survival of T1 and T2 vulval carcinoma patients.

The purpose of this study was to analyze (1) the prognostic factors for survival of T1 and T2 carcinoma patients and (2) the impact of the initial groin node status for the time to recurrence and site of recurrence. We performed a follow-up study on 190 women with a T1 or T2 squamous cell carcinoma of the vulva. Data were obtained on age and general medical condition, the clinical and histological characteristics of the primary tumor and the inguinofemoral lymph nodes, treatment, recurrences, and survival. The standard treatment was radical vulvectomy with bilateral inguinofemoral lymphadenectomy supplemented with postoperative radiotherapy to the primary site, groin, and pelvic side walls if groin metastases were present. Compared to patients without lymph node metastases in the groin, the relative risk of dying within a given time period was estimated to be 2.47 (limits of the 95% confidence interval: 1.24, 4.93) and 9.69 (3.90, 24.03) for patients with unilateral and bilateral node metastases, respectively. The number of metastatic lymph nodes or their intra- or extranodal growth was not associated with survival. The relative risk of dying within a given time period was 2.71 (1.36, 5.40) for patients with a T2 tumor compared to those with a T1 tumor and 2.37 (1.31, 4.31) for patients with vasoinvasive growth compared to those without capillary-lymphatic tumor infiltration. Tumor thickness, differentiation grade, and multifocal growth did not determine survival. In the multivariate Cox regression analysis, the presence of inguinofemoral lymph node metastases proved to be the most important prognostic factor for patients' survival. Of the 119 patients who underwent lymphadenectomy but in whom no groin node metastases were found, 6 (5%) patients manifested an early recurrence (i.e., residual cancer or a recurrence within 2 years after the diagnosis). In contrast, of the 51 patients with histologically documented groin node metastases, 15 (29.4%) manifested an early recurrence and these recurrences appeared equally distributed over the primary site and other sites.(ABSTRACT TRUNCATED AT 400 WORDS)