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.