Search

Immunohistochemistry (IHC) is often critical for distinction between metastatic carcinomas of Mullerian organ and breast origin. Paired box family protein 8 (PAX8) has been described as a transcription factor highly specific to neoplasms derived from Mullerian organs, thyroid, and kidney. PAX8 IHC with polyclonal and monoclonal antibody reagents was performed on 27 primary and 22 metastatic breast carcinomas. Eight of 27 primary breast carcinomas (30%) were positive for PAX8 with the monoclonal antibody reagent only; 0 of 22 were polyclonal anti-PAX8 immunoreactive. Substantial numbers of metastases had positive immunoreactivity for polyclonal anti-PAX8 (23%). Each of these metastases and additional cases (45% total) also had positive immunoreactivity for monoclonal anti-PAX8, including 5 of 7 brain metastases. IHC with monoclonal anti-PAX8 was positive on 6 of 7 primary breast carcinomas corresponding to PAX8-positive metastases. Together, these results indicate a significant fraction of breast carcinoma metastases and corresponding primary neoplasms have immunoreactivity for PAX8, and positivity rates depend on the antibody used. Diagnoses of metastatic breast carcinoma were achieved with the aid of clinical history and additional IHC in cases of PAX8 immunoreactivity. Contextual interpretation is imperative for PAX8 IHC, particularly when the differential diagnosis includes metastatic breast carcinoma with limited diagnostic material available.

Proliferative index is a prognostic feature of invasive ductal carcinoma of the breast, and has more recently emerged as a predictor of ductal carcinoma in situ (DCIS) local recurrence and progression when used in combination with other predictive markers. Ki67 is the most commonly used immunohistochemical marker of proliferative index. However, high interobserver and interlaboratory variability has been reported, in part due to differences in staining methodologies, positivity thresholds, and approaches to quantification. Phosphohistone-H3 (pHH3) is a marker of mitotic activity that has emerged as a more reliable indicator of proliferation in other neoplasms. Quantification of proliferative index was compared in 48 cases of DCIS using Ki67 and pHH3 immunohistochemistry. A strong linear relationship between Ki67 and pHH3 quantification was observed (P<0.0001, R=0.75). Interobserver concordance was modestly higher for pHH3 than Ki67 proliferative indices. However, positive pHH3 staining was more dichotomous (either negative or uniformly positive) and specific for mitotic activity, and interpretation of pHH3 proliferative indices was significantly faster than that of Ki67. The strong correlation between pHH3 and Ki67 supports the use of this marker as a measure of proliferative activity in DCIS.