Immunohistochemical Staining for p16 and p53 in Premalignant and Malignant Epithelial Lesions of the Vulva

Abstract

Two distinct types of vulvar squamous cell carcinomas and their precursors, vulvar intraepithelial neoplasias (VIN), which differ in terms of clinical presentation and behavior, have been delineated. Human papillomavirus (HPV)-associated carcinomas are of basaloid or warty type, whereas tumors unrelated to HPV are usually keratinizing and differentiated. Thus, the major stratifying factor for vulvar carcinomas and VIN is their etiopathogenetic relationship with HPV. However, because of technical difficulties in confidently detecting HPV in tissues, this diagnosis is usually based on purely morphologic criteria, even though some overlap exists between these histologic types. Recently, the tumor suppressor protein p16 has been shown to be specifically overexpressed in HPV-related carcinomas and premalignant lesions of the uterine cervix, oral cavity, and anus, but the presence of p16 vulvar squamous lesions has not been examined. We have evaluated the immunohistochemical expression of p16 in a series of formalin-fixed, paraffin-embedded vulvar carcinomas and their putative precursors. p16 was strongly positive in all cases of basaloid/condylomatous VIN3 (30/30) and basaloid (7/7) and warty (3/3) carcinomas. In contrast, p16 was almost consistently negative in normal skin, squamous cell hyperplasia (0/20), lichen sclerosus (0/19), differentiated (simplex) VIN3 (0/11), verrucous carcinoma (0/2), and keratinizing squamous cell carcinoma (3/33, 9%). One of the keratinizing squamous cell carcinomas positive for p16 occurred in a 25-year-old woman and the other two were associated with small foci of basaloid VIN3 adjacent to the tumor, suggesting a probable relationship with HPV. p16 was positive in 6 of 10 of basal cell carcinomas. In conclusion, p16 immunostaining is a good discriminator between HPV-associated and HPV-unrelated vulvar carcinomas and VIN, although it cannot differentiate basaloid squamous and basal cell carcinoma.

Vulvar intraepithelial neoplasia and vulvar squamous cell carcinoma: a clinicopathologic study of 18 cases

“…However, in their series of 10 cases with verrucous carcinoma, Gaulco et al, found that all the cases were found to be HPV negative in in-situ DNA hybridization analysis performed by HPV 6/11, 16/18, 31/35/51 probes [17]. In addition, Santos et al, supported the study of Gaulco et al, by their studies stating that p53 was negative in all the verrucous carcinoma cases [11,17]. In our study, in contrast to the studies mentioned above, p53 showed low grade positivity (1+), but in accordance with the cases in literature, Ki-67 proliferation index was rather low (6%) and p16 was negative.…”

“…The patients in this group typically develop a conventional (keratinizing) type ISCC associated with lichen sclerosis (LS) and squamous hyperplasia (SCH), and recent studies have shown the relationship with differentiated (simplex) VIN. Moreover, mutation in p53 tumor suppressing gene has often been observed [1,2,10,11].…”

P16INK4aImmunostaining but Lack of Human Papilloma Virus Type 16 in Cutaneous Squamous Cell Carcinoma and Basal Cell Carcinoma: a Report from West Iran

“…One study (Conscience et al, 2006), reported that p16 overexpression was significantly observed in 58% of cutaneous carcinomas (SCC:60% and BCC:50%) versus 0% of normal human skin. In another study (Santos et al, 2004), p16 was positive in 60% of BCCs and 91% in keratinizing SCC.…”

Phosphorylated S6 as an immunohistochemical biomarker of vulvar intraepithelial neoplasia

“…Full or near full thickness p16 INK4A immunostaining characterizes most classic VINs, but normal and hyperplastic vulvar epidermis, lichen sclerosus, and differentiated VIN are usually p16 negative. 17,18 Presence of strongly p53-positive suprabasal cells was proposed as an aid for the diagnosis of differentiated VIN 20 but this marker is not considered highly sensitive. Independent studies found a range of 54 to 83% of differentiated VINs to have abnormal p53 immunostaining patterns.…”

“…Immunohistochemical analysis for abnormal patterns of p16 INK4A , p53, and MIB1/Ki-67 expression, separately or as a panel, can distinguish classic from differentiated VIN but these markers often fail to identify the latter. [17][18][19][20] We therefore sought to find a more reliable biomarker for differentiated VIN.…”