Overexpression of p53 is correlated with stromal invasion in extramammary Paget's disease of the vulva.

Molecular alterations that are associated with clinicopathological features of extramammary Paget's disease of the vulva (PDV) are poorly understood. Consequently, we have investigated whether a correlation exists between overexpression of p53 protein and various clinicopathologic features of PDV. Our study group comprises 10 primary noninvasive PDVs, 3 primary PDVs with minimal invasion, and 1 primary PDV with frank invasion. Recurrence in the form of noninvasive PDV was seen in 4 patients with previously noninvasive PDVs and in 1 patient who previously had PDV with minimal invasion. Metastases to the inguinal lymph nodes were associated with the 1 PDV with frank invasion and 1 of the PDVs with minimal invasion. An immunohistochemical study of p53 expression was performed on paraffin-embedded tissue. Negative p53 immunostaining was seen in all of the primary noninvasive PDVs as well as their recurrences. Positive p53 immunostaining was observed in the invasive as well as the intraepidermal components of all of the primary PDVs with invasion, the metastatic tumors in the inguinal lymph nodes, and the recurrent PDV associated with prior invasion, indicating a possible role of p53 in the progression of PDV. To our knowledge, our observation of p53 overexpression in the intraepidermal component of PDVs associated with invasion is the first to be reported in the literature. This observation may prove helpful in identifying stromal invasion in small biopsies. We also report for the first time an association between high nuclear grade in PDV and the propensity for inguinal lymph node metastasis.