Immunophenotyping And Prognosis Of Mucinous Micropapillary Carcinomas Of The Breast

ObjectiveSince the first report about five patients of mucinous micropapillary carcinoma(MUMPC) by Ng in 2002. MUMPC has recently come to attention as sharing the same micropapillary feature with invasive micropapillary carcinoma(IMPC). Only a limited of literatures have reported about MUMPC, and due to small sample and limited follow-up time, most of them inferred its prognosis based on clinical and pathological features. There were also no clearly classification; it should be classified as micropapillary subtypes of mucinous carcinoma or mucinous subtypes of IMPC, or as an independent subtype between the two types, it is still unclear. This study compared MUMPC with conventional pure mucinous carcinoma(p MC) without micropapillary patterns and IMPC to analysis clinical pathological features, prognosis immunophenotyping and classification of MUMPC, so as to provide the basis for pathological diagnosis and clinical treatment.MethodsA retrospective evaluation of 531 cases pure mucinous carcinoma(p MC) from 2003-01 to 2012-12 was performed; cases with micropapillary patterns(MUMPC) and conventional pure mucinous carcinoma(p MC) without micropapillary patterns were selected. 134 cases MUMPC were selected as research group, 397 cases conventional p MC and homochronous 281 cases IMPC were selected as control groups. Clinicopathological characteristics, survival analysis and prognosis were compared among three groups, and factors that influencing lymph node metastasis of p MC, disease-free survival, overall survival of p MC and MUMPC also were studied. The expression of secreted mucins and neuroendocrine indicators were detected through immunohistochemistry in 32 cases MUMPC, 89 cases conventional p MC and 44 cases IMPC which randomly selected from the above cases, combined with ER, PR and HER-2 to identify discriminating immunophenotyping among three groups.Results1. Compared with the control group of conventional pMC, MUMPC were younger in ages, median ages only 46, and had a higher lymph nodemetastasis rates(P<0.001), exhibited increased lymphovascular invasion(P<0.001) and higher positive rates of HER-2(P<0.001), but have no differences in tumor size and nuclear grade.2. Compared with IMPC, MUMPC were younger in ages(P<0.001), but IMPC were larger in size(P=0.002), had a higher lymph node metastasis rates(P<0.001), and exhibited increased lymphovascular invasion(P<0.001), higher nuclear grade(P<0.001), and showed higher positive rates of HER-2(P<0.001) than MUMPC. Most nuclear grade of MUMPC were lower, about 75.4%(101/134), and there were statistically significant differences in nuclear grade and lymph node metastasis, moderates-high grade nuclear showed higher lymph node metastasis rates(P<0.001).3. Univariate logistic regression showed that age, tumor size, lymphovascular invasion, nuclear grade and MUMPC were the factors influencing lymph node metastasis of p MC, and multivariate analyses showed that age, tumor size, lymphovascular invasion and MUMPC were the independent factors for lymph node metastasis of p MC.4. Cox univariate analyses for DFS of p MC showed that tumor size, lymph node status, nuclear grade and MUMPC were impact factors, and multivariate analyses showed that those indicators also were independent factors for DFS of p MC.5. Cox univariate analyses for OS of p MC showed that lymph node status and nuclear grade were impact factors, and multivariate analyses showed that both of them also were the independent factors for p MC.6. Cox univariate analyses for DFS of MUMPC showed that age, tumor size, lymph node status, nuclear grade and HER-2 were impact factors, and multivariate analyses showed that all of them were independent factors for MUMPC, except for tumor size.7. Cox univariate analyses for OS of MUMPC showed that tumor size, lymph node status, nuclear grade and HER-2 were impact factors; multivariate analyses showed that all of them also were independentfactors for OS of MUMPC, except for tumor size.8. The ER and PR positive rates of MUMPC was respectively 91.8%(123/134) and 83.6%(112/134). There were no statistically significant differences among MUMPC, conventional p MC and IMPC in hormone receptors, most of them belong to luminal subtypes. The positive rate of HER-2 in MUMPC was lower than that in IMPC but higher than that in conventional p MC(P =0.001).9. Similar expression of MUC2, MUC5 AC and MUC6 were observed between MUMPC and conventional p MC. The expression of MUC2 was higher in MUMPC than IMPC(P<0.001), but there were no differences in MUC5 AC and MUC6.10. In neuroendocrine differentiation, similar synaptophysin expressions were detected in MUMPC and IMPC. The positive rate of synaptophysin was higher in MUMPC than in conventional p MC(P=0.003).11. Kaplan-Meier analysis indicated that MUMPC showed poorer diseasefree survival(DFS) and overall survival(OS) compared to conventional p MC, but better than IMPC(P<0.001).Conclusions1. Age, tumor size, lymphovascular invasion and MUMPC were the independent factors for lymph node metastasis of p MC.2. Tumor size, lymph node status, nuclear grade and MUMPC were independent factors for DFS of p MC; lymph node status and nuclear grade were independent factors for OS of p MC.3. MUMPC was a type of mutinous carcinoma, which showed higher lymph node metastasis, more aggressive clinicopathological behavior and poorer prognosis.4. Compared with conventional p MC, MUMPC showed more aggressive biological behavior, but better than IMPC. Therefore, if classified them into conventional p MC, it could lead to inadequate treatment for part of patients; but if classified into IMPC, it could lead to excessive treatment.The clinical pathological features and prognosis of MUMPC prompted that we should give more attention on this tumor in clinical practice, so as to evaluate prognosis for patients with mutinous carcinoma, avoid insufficient or excessive treatment.5. For its adverse biological behavior, we should give more attention on MUMPC in clinical practice, especially for those patients, with younger ages, higher lymph node metastasis rates, moderates-high nuclear grade and higher HER-2 positive rates, should be given more active clinical treatment, so that the patients could benefit greatly.