Serous Carcinoma component championed by Heparin Binding-EGF Like Growth Factor (HB-EGF) Predisposing to Metastasis and Recurrence in Stage I Uterine Malignant Mixed Mullerian Tumor

摘要

The stage I uterine Malignant Mixed Mullerian Tumor (MMMT) shows different potential for progression. We reason that MMMTs with high grade carcinomatous component and positivity for HB-EGF are prone to recurrence/metastasis in the early stage. A retrospective clinical and histopathologic review with immunohistochemical staining for HB-EGF, EGFR, and integrin-α5 was performed for 62 surgically staged MMMT cases. Recurrence/metastasis (RM) is 6/18(33%) in stage I diseases. Of all the clinicopathologic variables and biomarkers analyzed for stage I MMMT, serous carcinomatous component [83% (5/6) versus 17% (1/12), p=0.0015] and HB-EGF expression [100% (6/6) versus 50% (6/12), p=0.0339] are significantly different between group with RM and without RM. The presence of serous carcinoma in all stages is: 83% (5/6) in stage I with RM, 8% (1/12) in stage I without RM, 20% (1/5) in stage II, 36.4% (8/22) in stage III and 64.7% (11/17) in stage IV; this is paralleled by HB-EGF expression of 100% (6/6), 50% (6/12), 40% (2/5), 50% (11/22) and 71% (12/17) with a correlation coefficient r=0.9131(p=0.027). HB-EGF and integrin-α5 are highly expressed in MMMTs bearing serous carcinoma component, compared to endometrioid and unclassifiable/miscellaneous subtypes (84.6%/47.6%/33.3%, p=0.025 for HB-EGF; and 61.5%/42.9%/20.0%, p=0.021 for integrin-α5). The EGFR positivity is comparable among the three subtypes (48.1%, 47.6% and 26.7%, p= 0.326). This study indicates that serous carcinomatous component championed by expression of HB-EGF predisposes to recurrence/metastasis in stage I MMMT. This process might involve integrin-α5 and does not seem to require overexpression of EGFR. Further study is required.