We previously reported that the presence of extensive retraction clefts (RC) in breast cancers correlates with increasing tumor size and grade as well as lymphatic tumor spread and predicts poor outcome. This study is a prospective validation of our prior results. Consecutive cases of invasive breast carcinoma (n=2742) were reviewed to determine the diagnoses, including histologic type, grade, presence of lymphovascular invasion (LVI), and extent of RC. No differences were found in the extent of RC between corresponding core needle biopsy and surgical samples. Extent of RC showed a significant correlation with tumor size, grade, LVI, and nodal metastasis in both core needle biopsy and surgical specimens. These associations remained significant in subset analyses of small (≤1 cm), node-negative and node-positive tumors. Extensive RC predicted poor recurrence-free (P<0.0001) and overall (P<0.0001) survival and remained significant in subset analyses of node-negative (P=0.0015 and 0.0021, respectively) and node-positive (P=0.0039 and 0.0214, respectively) cases. Carcinomas without LVI but extensive RC were associated with better outcome than carcinomas with LVI but worse than those without LVI and low RC. This prospective study confirms that the presence of extensive RC in invasive breast carcinomas correlates with aggressive tumor features and lymphatic tumor spread. Extensive RC appears to be an independent factor predictive of poor outcome in node-negative and node-positive disease. Our results support the hypothesis that RCs are the morphologic reflection of biological changes in tumor cells playing a role in lymphatic tumor spread and likely represent an early stage of LVI with similar clinical implications.
我们先前报告乳腺癌中出现广泛收缩裂隙（RC）与肿瘤体积增大、分级升高和淋巴管肿瘤播散有关并提示预后不良。本研究前瞻性验证我们先前的结果。回顾分析侵袭性乳腺癌的连续病例（n=2742）以确定诊断，包括组织学类型、分级、出现淋巴脉管侵犯（LVI）和RC的程度。相应粗针活检和外科样本中RC程度无差别。粗针活检和外科样本中，RC程度与肿瘤大小、分级、LVI和淋巴结转移显著相关。对体积小（≤1cm）、淋巴结阴性和淋巴结阳性肿瘤的亚组分析表明这些相关性仍然有意义。广泛RC预示无复发生存不良（p＜0.0001）和总体生存不良（p＜0.0001），并在淋巴结阴性（p值分别为0.0015 和0.0021）和淋巴结阳性（p值分别为0.0039 和0.0214）病例中仍然有意义。无LVI、但出现广泛RC的癌比伴LVI的癌预后好，但比无LVI且低RC的癌预后差。本前瞻性研究证实浸润性乳腺癌中出现广泛RC与侵袭性肿瘤特征和淋巴管肿瘤播散有关。广泛RC是淋巴结阴性和淋巴结阳性疾病预后不良的独立预后因素。我们的结果支持以下假说，即RCs是肿瘤细胞生物学改变的形态学反应，在肿瘤淋巴管播散中发挥作用，并可能代表具有相似临床意义的LVI的早期阶段。