p53 gene mutation in female genital tract carcinosarcomas (malignant mixed müllerian tumors): a clinicopathologic study of 74 cases.

Mutations of the p53 suppressor gene are involved in carcinogenesis by inactivating p53 protein (p53P), which is involved in normal cell growth control. Mutant p53P, detectable by immunohistochemistry due to longer half-life as compared to wild-type, is a marker for p53 gene mutation. Seventy-four female genital tract carcinosarcomas (FGTCSs) (41 of the heterologous type exhibiting 33 rhabdomyosarcomatous, 13 chondrosarcomatous, one osteosarcomatous, and one liposarcomatous component) were stained using two commercially available monoclonal antibodies: p53P, clone DO7 (p53P-DO7) and p53P, Ab-6 (p53P-P6). p53P-DO7 and p53P-P6 stained 33 and 36, respectively, of 56 endometrial, 8 of 11 ovarian, 2 of 5 cervical, and 2 of 2 fallopian tube carcinosarcomas. Considering all 74 FGTCSs, p53P-DO7 and p53P-P6 stained both the carcinomatous component (CC) and the sarcomatous component (SC) in 46% and 54%, the CC only in 9.5% and 8.1%, and the SC only in 5.4 and 2.7%, respectively. The two antibodies for p53P showed the following concordance for staining of FGTCSs (either CC or SC or both) (p53P-DO7/p53P-P6): +/+, 58%; +/-, 1.3%; -/+, 6.7%; -/-, 34%. p53P immunoreactivity was not associated with histological features or grade of the CC or SC. Clinical follow-up was available in 72 cases, which showed 48.5% and 70.8% of patients recurred or died of disease by 12 and 80 months, respectively. 20.8% of patients were disease-free after 19 to 307 months of follow-up (median, 62; mean, 92). The remaining 8.4% of patients were disease-free but had insufficient follow-up (< 1 year).(ABSTRACT TRUNCATED AT 250 WORDS)