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Aims: It has been suggested that p16 is overexpressed in uterine leiomyosarcomas in comparison with leiomyomas. In this study, p16 immunohistochemical expression was assessed in a variety of uterine smooth muscle tumours, including usual leiomyomas, leiomyoma variants, smooth muscle tumours of uncertain malignant potential (STUMPs) and leiomyosarcomas. The aim was to ascertain whether there are differences in p16 expression between these groups and whether p16 is of potential value in the assessment of problematic uterine smooth muscle neoplasms. p16 expression was also compared with that of p53 and MIB1., Methods and Results: Cases of usual leiomyoma (n = 10), leiomyoma variants (n = 27), STUMP (n = 4) and leiomyosarcoma (n = 22) were subject to p16, p53 and MIB1 immunohistochemistry. For p16, cases were evaluated with respect to both staining distribution and intensity. There was a statistically significant difference in p16 distribution (P < 0.001) and intensity (P = 0.001) between leiomyosarcomas and the other groups. There was no difference in p16 expression between usual leiomyomas, leiomyoma variants and STUMPs. There were also statistically significant differences in p53 (P = 0.014) and MIB1 (P < 0.001) immunoreactivity between leiomyosarcomas and the other groups., Conclusions: p16 is overexpressed in uterine leiomyosarcomas compared with leiomyomas, benign leiomyoma variants and STUMPs, suggesting that p16 may be implicated in the pathogenesis of malignant uterine smooth muscle neoplasms. p16, in combination with p53 and MIB1, may be of value as an adjunct to morphological examination in the assessment of problematic uterine smooth muscle tumours, although further large-scale studies with follow-up are necessary to confirm this.

Aims: A dualistic pathway of ovarian serous carcinogenesis is now well established whereby high-grade serous carcinoma and low-grade serous carcinoma represent two distinct tumour types with a different underlying pathogenesis. The aim of this study was to compare expression of p16 INK4A (p16) in these two tumour types. We also included cases of serous borderline tumour, since these are considered to represent a precursor lesion of low-grade serous carcinoma., Methods and Results: Cases of serous borderline tumour (n = 18), low-grade ovarian serous carcinoma (n = 22) and high-grade ovarian serous carcinoma (n = 24) were stained with a monoclonal antibody against p16. Cases were scored both with respect to intensity of immunoreactivity (weak, 1+; moderate, 2+; or strong, 3+) and distribution (0, negative or occasional positive cells; 1+, < 10% cells positive; 2+, 10-25% cells positive; 3+, 26-50% cells positive; 4+, 51-75% cells positive; or 5+, 76-100% cells positive). An immunohistochemical composite score was also calculated (0-15) by multiplying the intensity and distribution scores. There was a statistically significant difference in p16 immunoreactivity with respect to intensity, distribution and composite score between high-grade serous carcinoma and each of the other two groups, with the high-grade neoplasms exhibiting stronger and more diffuse positivity. Most high-grade serous carcinomas exhibited positivity of close to 100% of tumour cells. There was no significant difference in p16 expression between the borderline tumours and low-grade serous carcinomas., Conclusions: The increased expression of p16 in high-grade serous carcinoma compared with low-grade serous carcinoma and serous borderline tumour is in keeping with a different underlying pathogenesis. p16 may be implicated in the development of high-grade serous neoplasia within the ovary and elsewhere within the female genital tract.