1. Serous carcinomatous component championed by heparin-binding EGF-like growth factor (HB-EGF) predisposing to metastasis and recurrence in stage I uterine malignant mixed mullerian tumor.
- Author
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Zhang L, Shimizu D, Killeen JL, Honda SA, Lu D, Stanoyevitch A, Lin F, Wang B, Monuki ES, and Carbone M
- Subjects
- Aged, ErbB Receptors analysis, Female, Humans, Immunohistochemistry, Integrin alpha5 analysis, Middle Aged, Mixed Tumor, Malignant secondary, Mixed Tumor, Malignant surgery, Mixed Tumor, Mullerian secondary, Mixed Tumor, Mullerian surgery, Neoplasm Invasiveness, Neoplasm Staging, Neoplasms, Cystic, Mucinous, and Serous secondary, Neoplasms, Cystic, Mucinous, and Serous surgery, Retrospective Studies, Tissue Array Analysis, Treatment Outcome, Uterine Neoplasms pathology, Uterine Neoplasms surgery, Biomarkers, Tumor analysis, Cell Movement, Heparin-binding EGF-like Growth Factor analysis, Mixed Tumor, Malignant chemistry, Mixed Tumor, Mullerian chemistry, Neoplasm Recurrence, Local, Neoplasms, Cystic, Mucinous, and Serous chemistry, Uterine Neoplasms chemistry
- Abstract
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 disease. Of all the clinicopathologic variables and biomarkers analyzed for stage I MMMT, serous carcinomatous component (83% [5/6] versus 17% [1/12], P = .0015) and HB-EGF expression (100% [6/6] versus 50% [6/12], P=.0339) were significantly different between groups with RM and without RM. The presence of serous carcinoma in all stages was 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 was 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=.027). HB-EGF and integrin-α5 were highly expressed in MMMTs bearing serous carcinoma component, compared to endometrioid and unclassifiable/miscellaneous subtypes (84.6%/47.6%/33.3%, P=.025 for HB-EGF; and 61.5%/42.9%/20.0%, P=.021 for integrin-α5). The EGFR positivity was comparable among the three subtypes (48.1%, 47.6% and 26.7%, P=.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., (Published by Elsevier Inc.)
- Published
- 2016
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