Kanczuga-Koda Luiza, Sulkowska Mariola, Koda Mariusz, Rutkowski Ryszard, Sulkowski Stanislaw
Department of Medical and General Pathomorphology, Medical University of Bialystok, Poland.
Folia Histochem Cytobiol. 2007;45 Suppl 1:S175-80.
Gap junctions are specialized cell membrane channels composed of connexins (Cxs), which mediate the direct passage of small molecules between adjacent cells. They are involved in the regulation of cell cycle, cell signaling and differentiation as well as probably invasion and metastasis. Up to now, Cx32 status in human breast cancer has not been studied. Consequently, the aim of the present study was the evaluation of the expression of connexin 32 (Cx32) in primary breast tumors (PTs) and matched-paired metastases to lymph nodes (MLNs) in correlation with selected clinicopathological features. Tissue samples from 79 women were examined by immunohistochemistry, using the streptavidin-biotin-peroxidase complex technique for Cx32. Cytoplasmic expression of Cx32 was detected in 31 of 79 breast cancers (39.2%). Both epithelial and myoepithelial cells of normal ducts adjacent to the tumor did not express Cx32. Increased expression of studied Cx was observed in metastases to lymph nodes relative to primary tumors. Additionally, Cx32-negative primary tumors developed Cx32-positive metastases. Statistical comparisons of Cx32 expression in the matched pairs indicate that this protein significantly increased in lymph node metastases compared to primary tumors (p<0.001). The expression of Cx32 in primary breast cancer was not statistically associated with age of patients, tumor size, lymph node status, but we observed a tendency toward association between Cx32 expression and histological differentiation. In conclusion, transformed cells may have an ability to produce Cxs also atypical for normal cells. Increased expression of Cx32 in metastases to the lymph nodes might reflect alteration in connexin gene transcription during breast carcinogenesis and finally, it may be a sign of more malignant phenotype of cancerous cells.
缝隙连接是由连接蛋白（Cxs）组成的特殊细胞膜通道，介导小分子在相邻细胞间的直接传递。它们参与细胞周期、细胞信号传导和分化的调节，也可能与侵袭和转移有关。到目前为止，尚未对人乳腺癌中的Cx32状态进行研究。因此，本研究的目的是评估连接蛋白32（Cx32）在原发性乳腺肿瘤（PTs）和配对的淋巴结转移灶（MLNs）中的表达，并与选定的临床病理特征进行相关性分析。采用链霉亲和素-生物素-过氧化物酶复合物技术检测Cx32，对79名女性的组织样本进行免疫组织化学检查。在79例乳腺癌中有31例（39.2%）检测到Cx32的细胞质表达。肿瘤旁正常导管的上皮细胞和肌上皮细胞均不表达Cx32。相对于原发性肿瘤，在淋巴结转移灶中观察到所研究的Cx表达增加。此外，Cx32阴性的原发性肿瘤出现了Cx32阳性的转移灶。配对样本中Cx32表达的统计学比较表明，与原发性肿瘤相比，该蛋白在淋巴结转移灶中显著增加（p<0.001）。原发性乳腺癌中Cx32的表达与患者年龄、肿瘤大小、淋巴结状态无统计学关联，但我们观察到Cx32表达与组织学分化之间存在关联趋势。总之，转化细胞可能具有产生正常细胞中也不典型的Cxs的能力。淋巴结转移灶中Cx32表达的增加可能反映了乳腺癌发生过程中连接蛋白基因转录的改变，最终，它可能是癌细胞更恶性表型的一个标志。
