Altered Rb, p16, and p53 expression is specific for porocarcinoma relative to poroma

Abstract

Background Porocarcinomas are rare aggressive carcinomas that harbor tumor suppressor mutations and must be distinguished from benign entities such as poromas. Methods To determine whether altered expression of these genes was diagnostically informative, we examined p53, Rb, and p16 staining patterns in 15 poromas and 16 porocarcinomas. Results Poromas consistently displayed diffuse strong expression of Rb in all but one case that displayed focal loss (1/15, 7%), and no evidence of aberrancy in p53 or p16. Porocarcinomas displayed diffuse or focal loss of Rb expression in 9/16 (56%) cases, diffuse loss or overexpression of p53 in 8/15 (53%), and diffuse loss or overexpression of p16 in 6/14 (43%). Diffuse aberrancy in p53 and Rb expression correlated with tumor mutations in TP53 and RB1, respectively, whereas focal Rb loss was associated with wild type RB1. Diffuse p16 overexpression correlated with Rb loss rather than CDKN2A mutation. For porocarcinomas with all three stains evaluable, 10/13 (77%) displayed aberrancy in at least one marker. Conclusions Our findings suggest that altered p53, p16, and/or Rb expression is relatively specific to porocarcinoma in comparison with poroma. Technical limitations of this panel, including possible focal Rb loss, must be kept in mind, especially in limited samples.

Utility of YAP1 and NUT immunohistochemistry in the diagnosis of porocarcinoma

“…The diagnosis remains primarily a morphologic one as there are no reliable and specific immunohistochemical markers available. Both p53 and p16, for example, may be overexpressed in porocarcinoma, but are also overexpressed in squamous cell carcinoma 6‐9 …”

A case of YAP1 and NUTM1 rearranged porocarcinoma with corresponding immunohistochemical expression: Review of recent advances in poroma and porocarcinoma pathogenesis with potential diagnostic utility

“…24,25 Thus, aberrancies in the expression of the corresponding immunohistochemical markers could also support the diagnosis of porocarcinoma. 26 By IHC, Sekine et al 6 However, the C-terminus antibody was not available for immunohistochemical analysis, so we cannot draw conclusions on YAP1 rearrangement solely based on YAP1 N-terminus positivity. Nuclear and/or cytoplasmic immunoreaction of YAP1 has also been reported in squamous cell carcinomas and their precursors, as well as basal cell carcinomas 27,28,29,30 (Table 1), thus the marker is not entirely specific for poromas and porocarcinomas.…”

An atypical chondroid syringoma with malignant degeneration: Utility of comparative genomic hybridization in confirming the diagnosis

“…In this case, the presence of considerable copy number changes (n = 14) combined with the morphologic atypia observed and demonstrable clonal evolution with loss of 17p ( TP53 ) and LOH on 16q (likely reflecting loss of another tumor suppressor gene) support a diagnosis of malignant transformation. In particular, loss of TP53 is known to be associated with disease progression and an adverse prognostic impact in multiple settings including other cutaneous adnexal neoplasms 22,23 . Additional larger studies examining the cytogenetic changes in benign CS, atypical CS, and bona fide malignant CS are needed before firm conclusions can be drawn regarding the exact number/threshold or consistent genetic events that are associated with aggressive behavior in this context.…”

“…In particular, loss of TP53 is known to be associated with disease progression and an adverse prognostic impact in multiple settings including other cutaneous adnexal neoplasms. 22,23 Additional larger studies examining the cytogenetic changes in benign CS, atypical CS, and bona fide malignant CS are needed before firm conclusions can be drawn regarding the exact number/threshold or consistent genetic events that are associated with aggressive behavior in this context.…”