A comparison of p53 and WT1 immunohistochemical expression patterns in tubo-ovarian high-grade serous carcinoma before and after neoadjuvant chemotherapy

Abstract

Aims

Treatment of patients with tubo-ovarian high-grade serous carcinoma (HGSC) is increasingly based on diagnosis on small biopsy samples and the first surgical specimen is often post-chemotherapy. p53 and WT1 are important diagnostic markers for HGSC. The effect of neo-adjuvant chemotherapy on p53 and WT1 expression has not been widely studied. We aimed to compare p53 and WT1 expression in paired pre- and post-chemotherapy samples of HGSC.

Methods and Results

Immunohistochemistry (IHC) was carried out for p53 and WT1 on paired omental HGSC samples pre- and post-chemotherapy. p53 IHC was recorded as normal (wild-type) or abnormal (mutation-type), further classified as overexpression, complete absence or cytoplasmic, and for WT1 as positive or negative. A subset of cases was further assessed for the extent of nuclear immunoreactivity of WT1 using the H-score.

57 paired samples were stained with p53. 56/57 (98%) cases showed mutation-type p53 staining. Pre- and post-chemotherapy IHC results were concordant in 55/57 (96%) cases. For WT1, pre- and post-chemotherapy IHC results were concordant in 56/58 (97%) of cases. In 23 paired WT1 cases the mean post-treatment H-score decreased from 227 (range 20-298, SD 64) to 151 (range 0-288, SD 78) (p=0.0008).

Conclusions

Immunohistochemical expression of p53 (abnormal/mutation-type pattern) and WT1 in HGSC is almost universal and largely concordant before and after chemotherapy. This finding underscores the reliability of these diagnostic markers in small samples and in surgical samples following neo-adjuvant chemotherapy with very few exceptions. A novel finding was the significant diminution in intensity of WT1 staining following chemotherapy.

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