乳腺浸润性微乳头状癌的临床病理学特征及HGF/c-Met蛋白的表达
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摘要
乳腺浸润性微乳头状癌是一种特殊类型乳腺癌,为揭示乳腺浸润性微乳头状癌的形态学与生物学特点,本文应用回顾性分析、免疫组织化学染色及统计学方法研究乳腺浸润性微乳头状癌的临床病理学特征,分析HGF与受体c-Met在乳腺浸润性微乳头状癌的表达,及其与临床病理学特征的关系。
     本文研究结果如下:(1)乳腺浸润性微乳头状癌在乳腺癌中的发病率为4.18%,其淋巴管侵犯率、淋巴结转移率及转移个数均明显高于浸润性导管癌(P<0.01)。(2)乳腺IMPC组织中c-Met的表达值较浸润性导管癌明显增高(P<0.05),IMPC组织HGF的表达值与浸润性导管癌无显著差别(P>0.05)。HGF表达阳性组c-Met的表达值明显高于HGF阴性组c-Met的表达值(P<0.05)。(3)c-Met蛋白的表达值与IMPC的组织学分级、病理学分期有关(P<0.05)。(4)HGF蛋白的表达值与IMPC的组织学分级有关(P<0.05)。
     本文研究得出以下结论:(1)乳腺IMPC淋巴管侵犯和区域淋巴结转移明显高于浸润性导管癌,淋巴管侵犯和区域淋巴结转移是IMPC的显著生物学特点。(2)本文首次研究了HGF和c-Met蛋白在乳腺IMPC中的表达,c-Met蛋白在IMPC组织中过表达。(3)c-Met蛋白在IMPC中的过度表达与IMPC的组织学分级、病理学分期有关,c-Met可以作为判断IMPC预后的因素之一。(4)HGF蛋白的表达与IMPC的组织学分级有关。
Breast cancer is one of the most common malignant tumors and its incidence rate among women is in the first place. It seriously threats the health and lives of female patients. Invasive micropapillary carcinoma (IMPC) is one of rare histological types of breast cancer. Because of its lower incidence rate and frequently mixed existence with invasive ductal carcinoma in histology, the tumor is often misdiagnosed to other types of invasive breast carcinoma by pathologists. Previous studies showed that there were different results about histological diagnostic criteria, clinical and pathologic features of IMPC and prognosis of the patients. There are fewer studies about IMPC of breast in our county, and most of them are case reports. Hepatocyte growth factor (HGF) and its receptor c-Met protein are involved in the oncogenesis of many malignant tumors, in particularly, closely related with the invasion and metastasis of tumors. There aren’t yet reports of the expression of HGF/c-Met proteins in breast IMPC in the world so far. Therefore, in order to investigate the clinicopathologic features of IMPC of the breast, the clinical and pathological data of breast cancer in our hospital in the past five years were reviewed and evaluated retrospectively. Meanwhile immunohistochemical staining was performed to detect the expression of HGF and its receptor c-Met protein in breast IMPC, and the relationship between expression of these proteins and the pathologic features was statistically analyzed. This study will provide a theoretical basis for further research of the biological behavior and the individual treatment of the tumor.
     The results are as follows:
     (1)Twenty cases of IMPC (4.18%, 20/478)were diagnosed. There weren’t significant differences in the patients’age and tumor size between IMPC and IDC(P>0.05).
     (2) 6 cases were simple IMPC, accounting for 30% and the other 14 caseswere mixed IMPC in histology. The mixed types usually were accompanied with IDC and carcinoma in situ.
     (3) The incidences of lymphovascular infiltration(65%, 13/20) and regional lymph node metastase(s90%,18/20)were significantly higher in IMPC than those in IDC, the number of positive lymph nodes (mean 6.65±5.24) was also significantly higher in IMPC compared with those in IDC(P<0.01).
     (4) There were no significant differences of the positive expression rates of ER, PR, HER-2, p53 and Ki67 in IMPC compared with that in IDC (P>0.05).
     (5) The expression values of c-Met in IMPC were evidently higher than that in IDC (P<0.05), Moreover, the expression values of c-Met were larger when there were larger expression values of HGF in tumor cells (P<0.05). There was no correlation in expression values of HGF btween in IMPC and in IDC (P>0.05).
     (6) The expression values of c-Met were closely related with the histological grading and pathological stage of IMPC (P<0.05). The higher the histological grading and pathologic stage, the greater the expression values of c-Met.
     (7) The expression values of HGF were closely related with the histological grading of IMPC (P<0.05). The higher the histological grading, the greater the expression values of HGF.
     The conclusions are as follows:
     (1) The incidences of lymphovascular infiltration and regional lymph node metastases were significantly higher in IMPC than in IDC. This study showed that lymphovascular infiltration and regional lymph node metastasis were notable biological features of breast IMPC.
     (2)This study was the first to detect the expression of HGF and c-Met proteins in the tissue of breast IMPC. It was revealed that c-Met protein was over-expressed in IMPC.
     (3) The expression level of c-Met was closely correlated with the histological grading and pathologic stage of IMPC. The study showed that the level of c-Met protein would be used as one of the prognostic factors of IMPC.
     (4) The expression level of HGF was closely correlated with the histological grading of IMPC, it need to be further substantiated by research whether HGF could be used as a prognostic indicator of IMPC.
     The clinicopathologic features and the expression of HGF/c-Met in breast IMPC had been shown in this study. It provided theoretical basis to fully understand the biological characteristics and the mechanisms of invasion and metastasis of breast IMPC.
引文
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