Kramer Zsófia, Budai András, Pesti Adrián, Kulka Janina, Tőkés Anna-Mária
Department of Pathology, Forensic and Insurance Medicine, Semmelweis University, Budapest, Hungary.
Pathol Oncol Res. 2024 Dec 2;30:1611987. doi: 10.3389/pore.2024.1611987. eCollection 2024.
Invasive micropapillary carcinoma of the breast is characterized by clusters of cells presenting with inverted polarity. Although the apico-basal polarity is a fundamental property of the epithelium, the biological alterations leading to the inside-out pattern observed in invasive micropapillary carcinoma (IMPC) remain mostly unknown. The regulation of tight junctions in polarity formation and maintenance is acknowledged. By using immunohistochemistry, we have analysed claudin-1, -3, -4, and -7 tight junction proteins expression and their prognostic value on IMPCs and compared them to invasive breast carcinomas of no special type (IBC-NST) tumors. Our cohort consisted of 37 IMPCs, 36 IBC-NST and 9 mixed IMPC/IBC-NST tumors. Two scoring systems were used to quantify protein expression: a 4-tier scoring system and the H-score method. Distant metastasis free survival (DMFS) intervals and overal survival (OS) data were used for prognosis evaluation. The analysed samples were characterized mainly by low or no claudin-1 expression whereas claudins-3, -4 and -7 showed variable positivity. We have found no significant differences in claudin-3 and -4 protein expression between IMPC and IBC-NST groups with either scoring methods, however high claudin-7 expression was found in significantly more IMPCs than IBC-NST tumors according to the H-score system ( = 0.02). The 4-tier scoring method revealed association of claudin-7 expression with molecular tumor subtypes ( = 0.001). IMPC and IBC-NST tumors did not show difference in DMFS ( = 0.70). In the analysis of pure IMPC and IBC-NST tumors, positive/high claudin-4 protein expression was significantly associated with shorter DMFS ( = 0.02/ = 0.008, respectively according to the two scoring methods). Claudin-3 and claudin-7 expression showed no association with DMFS or OS. Changes in epithelial polarity seem not to be related to claudin-1, -3, and -4 expression. Increased claudin-4 expression may have a role in breast cancer progression.
乳腺浸润性微乳头状癌的特征是细胞簇呈现极性倒置。尽管顶端-基底极性是上皮细胞的基本特性，但导致浸润性微乳头状癌（IMPC）中出现由内向外模式的生物学改变仍大多未知。紧密连接在极性形成和维持中的调节作用已得到认可。通过免疫组织化学，我们分析了闭合蛋白-1、-3、-4和-7紧密连接蛋白的表达及其对IMPC的预后价值，并将它们与非特殊类型浸润性乳腺癌（IBC-NST）肿瘤进行比较。我们的队列包括37例IMPC、36例IBC-NST和9例混合性IMPC/IBC-NST肿瘤。使用两种评分系统来量化蛋白表达：四级评分系统和H评分法。远处无转移生存期（DMFS）和总生存期（OS）数据用于预后评估。分析的样本主要特征为闭合蛋白-1表达低或无表达，而闭合蛋白-3、-4和-7显示出不同程度的阳性。我们发现，无论采用哪种评分方法，IMPC组和IBC-NST组之间闭合蛋白-3和-4的蛋白表达均无显著差异，然而，根据H评分系统，IMPC中闭合蛋白-7高表达的比例显著高于IBC-NST肿瘤（P = 0.02）。四级评分法显示闭合蛋白-7表达与分子肿瘤亚型相关（P = 0.001）。IMPC和IBC-NST肿瘤在DMFS方面无差异（P = 0.70）。在纯IMPC和IBC-NST肿瘤分析中，闭合蛋白-4蛋白表达阳性/高表达与较短的DMFS显著相关（根据两种评分方法，分别为P = 0.02/P = 0.008）。闭合蛋白-3和闭合蛋白-7的表达与DMFS或OS均无关联。上皮极性的改变似乎与闭合蛋白-1、-3和-4的表达无关。闭合蛋白-4表达增加可能在乳腺癌进展中起作用。
