HOXB8 expression in ovarian serous carcinoma effusions is associated with shorter survival

Abstract

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Highlights

► HOXB5 and HOXB8 are differentially expressed at various anatomic sites in serous ovarian carcinoma.
► HOXB5 expression is higher in post-chemotherapy disease recurrence effusions compared to pre-chemotherapy primary diagnosis effusions.
► Higher HOXB8 expression in effusions is associated with shorter overall and progression-free survival in serous ovarian carcinoma.

Objective

HOX proteins are key transcription factors in embryogenesis. HOXB5 and HOXB8 were previously shown to be overexpressed in ovarian/primary peritoneal serous carcinoma compared to breast carcinoma using gene expression arrays. The present study investigated the clinical role of HOXB5 and HOXB8 in advanced-stage (FIGO III–IV) ovarian serous carcinoma.

Methods

HOXB5 and HOXB8 protein expression was analyzed in 286 effusions and 76 patient-matched solid lesions (27 primary carcinomas, 49 metastases) using immunohistochemistry. Expression was analyzed for association with clinicopathologic parameters, including survival.

Results

Cytoplasmic HOXB5 protein was detected in 268/286 (94%) effusions. HOXB8 was expressed at both the cytoplasm (252/286; 88%) and nucleus (131/286; 46%) of carcinoma cells. Cytoplasmic HOXB5, cytoplasmic HOXB8 and nuclear HOXB8 were found in 56/76 (74%), 76/76 (100%) and 30/76 (39%) solid lesions, respectively, with significantly higher HOXB5 expression in effusions (p = 0.002) and higher cytoplasmic HOXB8 in solid lesions (p < 0.001). HOXB5 expression was higher in post-chemotherapy disease recurrence effusions compared to pre-chemotherapy effusions tapped at diagnosis (p = 0.04). In univariate survival analysis of the effusion cohort, higher expression of cytoplasmic HOXB8 was associated with significantly shorter progression-free survival (p = 0.033), whereas higher nuclear HOXB8 expression was associated with significantly shorter overall survival in analysis limited to patients with post-chemotherapy effusions (p = 0.036). Neither finding was independent prognostic factor in Cox multivariate analysis.

Conclusions

HOXB5 and HOXB8 are frequently expressed in ovarian serous carcinoma, with anatomic site-related differences for cytoplasmic staining. HOXB5 may be affected by chemotherapy in effusions. HOXB8 expression is associated with shorter survival in metastatic serous carcinoma.