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Clinicopathological Features and Lymph Node Metastasis-related Factors of Primary Neuroendocrine Breast Cancer and Invasive Breast Cancer of Nonspecial Type: A Case-control Study
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摘要:
目的 探讨原发性乳腺神经内分泌癌(primary neuroendocrine breast carcinoma, pNEBC)的临床病理特点以及淋巴结转移相关影响因素，为pNEBC的治疗及预后评价提供依据。 方法 回顾性选取2004年11月至2016年10月于北京协和医院乳腺外科手术治疗并诊断为pNEBC的患者为研究组(pNEBC组)，1:4配对同期手术并诊断为乳腺浸润性癌(非特殊型)(invasive carcinoma of no special type，NST)的患者为对照组(NST组)，比较两组患者的临床病理特点及淋巴结转移相关影响因素。 结果 共50例符合纳入和排除标准的pNEBC患者入选本研究，按照1:4配对原则入选同期NST患者200例。两组患者年龄、瘤体直径、组织学分级、淋巴结清扫数目及TNM分期均无统计学差异(P均＞0.05)。pNEBC组淋巴结转移15例(30.0%，15/50)；雌激素受体(estrogen receptor，ER)阳性表达率为96.0%(48/50)，孕激素受体(progesterone receptor，PR)阳性表达率为84.0%(42/50)，人表皮生长因子受体2(human epidermal growth factor receptor-2，Her-2)阳性表达率为10.4%(5/48)，嗜铬素A阳性表达率为58.0%(29/50)，突触素阳性表达率为97.9%(47/48)。对于影响淋巴结转移的相关因素，组织学分级、ER表达、PR表达、Her-2表达、Ki-67指数、分子分型差异在两组中均无统计学意义(P均＞0.05)，T分期在NST组患者中存在显著差异(P=0.006)，在pNEBC组中无显著差异(P=0.872)。 结论 pNEBC患者ER、PR阳性表达率高，Her-2阳性表达率低，突触素阳性表达率较嗜铬素A高，其生物学行为尚需进一步研究，联合检测上述免疫组化指标并结合淋巴结状况，可能有助于pNEBC的预后评估。 Abstract:Objective This study aimed to approach the clinicopathological characteristics of primary neuroendocrine breast carcinoma(pNEBC) and to identify related factors of lymph node metastasis. Methods We retrospectively collected the clinical data of patients in Department of Breast Surgery, Peking Union Medical College Hospital from November 2004 to October 2016.The patients who were diagnosed as pNEBC were selected as the study group (pNEBC group). Meanwhile, the patients who were operated at the same time and diagnosed as invasive carcinoma of no special type(NST) were selected as the control group (NST group). The clinico-pathological characteristics and lymph node metastasis-related factors of the two groups were compared. Results Following the inclusion and exclusion criteria, a tolal of 50 patients diagnosed as pNEBC and 200 patients diagnosed as NST were included in this study.There was no significant difference in age, tumor diameter, histological grade, number of lymph nodes dissected, and TNM stage between the two groups (all P > 0.05). The baseline level of the two groups was similar. Fifteen pNEBC patients(30.0%, 15/50) had lymph node metastasis. The expressions of estrogen receptor(ER), progesterone receptor(PR), and human epidermal growth factor receptor-2(Her-2) status were 96.0%, 84.0%, and 10.4%, respectively. The expressions of chromogranin A(CgA) and synaptophysin(Syn) were 58.0% and 97.9%, respectively. In the analysis of related factors affecting the lymph node metastasis, there was no significant difference in the histological grade, immunohistochemical index, and molecular typing between the two groups(all P > 0.05). There existed significant differences in the T stage in the control group (P=0.006), while no difference found in the study group (P=0.872). Conclusions pNECB is often positive for hormone receptors, but almost negative for Her-2. The positive expression rate of Syn is higher than that of CgA. Although interfering factors on the prognosis of pNEBC are still controversial, its biological behavior needs further study and more attention should be paid to joint detection of the above immunohistochemical indicators and lymph node status. 利益冲突 无 -
图 1 乳腺原发性神经内分泌癌的镜下表现(×150)
A.HE染色可见大量癌细胞，呈管状及小梁状结构；B.免疫组化染色ER，肿瘤细胞呈强阳性；C.免疫组化染色PR，肿瘤细胞中度阳性；D.免疫组化染色Her-2，肿瘤细胞无明显着色；E.免疫组化染色嗜铬素A，肿瘤细胞弥漫阳性；F.免疫组化染色突触素，肿瘤细胞弥漫阳性
表 1 pNEBC组与NST组患者临床特征比较*
临床特征 pNEBC组(n=50) NST组(n=200) P值 年龄(x±s，岁) 56.4±13.7 54.9±12.8 0.453 肿瘤最大直径[n(%)] 0.141 ≤2 cm 29(59.2) 137(68.8) ＞2~5 cm 18(36.7) 60(30.2) ＞5 cm 2(4.1) 2(1.0) 组织学分级[n(%)] 0.013 Ⅰ 14(35.0) 27(15.0) Ⅱ 17(42.5) 95(52.8) Ⅲ 9(22.5) 58(32.2) 淋巴结清扫数目(x±s，个) 18.61±9.66 16.71±9.36 0.249 淋巴结转移数目[n(%)] 0.869 0 26(63.4) 106(65.0) 1~3个 8(19.5) 27(16.6) 4~9个 4(9.8) 21(12.9) ≥10个 3(7.3) 9(5.5) TNM分期[n(%)] 0.077 Ⅰ 14(35.0) 68(41.2) Ⅱ 18(45.0) 65(39.4) Ⅲ 6(15.0) 32(19.4) Ⅳ 2(5.0) 0(0) *分组统计中存在部分病例资料缺失，按实际数量进行统计；pNEBC：原发性乳腺神经内分泌癌；NST：乳腺浸润性癌(非特殊型) 
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表 2 50例pNEBC患者淋巴结转移率影响因素分析*
指标 淋巴结转移率[%(n/N)] P值 T分期 0.872 T1 33.3(6/18) T2 42.1(8/19) T3/ T4 50.0(1/2) 组织学分级 0.229 Ⅰ 14.3(2/14) Ⅱ 41.2(7/17) Ⅲ 22.2(2/9) ER表达 1.000 阳性 35.9(14/39) 阴性 50.0(1/2) PR表达 0.639 阳性 33.3(11/33) 阴性 50.0(4/8) Her-2表达 0.871 阳性 44.4(4/9) 阴性 34.4(11/32) Ki-67指数 0.753 ＜14% 35.3(6/17) ≥14% 40.9(9/22) 分子分型 0.865 Luminal A型 30.8(4/13) Luminal B型 40.9(9/22) 三阴性 50.0(1/2) *分组统计中存在部分病例信息缺失，按照实际数量进行统计；pNEBC：同表 1；ER：雌激素受体；PR：孕激素受体；Her-2：人表皮生长因子受体2
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表 3 200例NST患者淋巴结转移率影响因素分析*
指标 淋巴结转移率[%(n/N)] P值 T分期 0.006 T1 25.6(23/90) T2 47.1(32/68) T3/ T4 66.7(2/3) 组织学分级 0.098 Ⅰ 14.8(4/27) Ⅱ 30.5(29/95) Ⅲ 37.9(22/58) ER表达 0.090 阳性 38.7(48/124) 阴性 23.7(9/38) PR表达 0.381 阳性 33.3(41/123) 阴性 41.0(16/39) Her-2表达 0.692 阳性 37.5(9/24) 阴性 33.3(44/132) Ki67指数 0.648 ＜14% 31.7(13/41) ≥14% 35.7(41/115) 分子分型 0.908 Luminal A型 30.8(12/39) Luminal B型 37.1(33/89) Her-2过表达型 33.3(2/6) 三阴性 30.0(6/20) *分组统计中存在部分病例信息缺失，按照实际数量进行统计；NST：同表 1；ER、PR、Her-2：同表 2
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