Shinto Eiji, Tsuda Hitoshi, Ueno Hideki, Hashiguchi Yojiro, Hase Kazuo, Tamai Seiichi, Mochizuki Hidetaka, Inazawa Johji, Matsubara Osamu
Department of Pathology II, National Defense Medical College, Tokorozawa, Japan.
Lab Invest. 2005 Feb;85(2):257-66. doi: 10.1038/labinvest.3700199.
The laminin-5 gamma 2 chain (LN-5gamma2) is known to be a marker of invasion in several cancer types. Our purpose was to examine the prognostic significance of LN-5gamma2 expression in different areas of individual colorectal cancers (CRCs) by using tissue microarrays (TMAs), and to clarify the optimal areas for prognostic assessment. Using formalin-fixed paraffin-embedded tissue blocks of pT3 primary CRCs resected from 120 patients, we constructed TMA blocks of tissue core specimens taken from the submucosal invasive front, subserosal invasive front, central area, and rolled edge of each tumor. Using these four-point TMA sets, cytoplasmic LN-5gamma2 expression was immunohistochemically surveyed, and the area-specific prognostic significance of LN-5gamma2 expression was evaluated. The data revealed that 35, 30, 15 and 10% of the 120 CRCs showed high-grade LN-5gamma2 expression in the submucosal invasive front, subserosal invasive front, central area and rolled edge, respectively. Disease-specific survival curves for the groups with high- and low-grade LN-5gamma2 in the submucosal invasive front and subserosal invasive front were different significantly or of marginal difference (respective 5-year survival rates: 54 and 78% for submucosal invasive front (P=0.030) and 58 and 75% for subserosal invasive front (P=0.055)). Multivariate analysis revealed that the grades of LN-5gamma2 expression in submucosal invasive front (hazard ratio=2.0, P=0.047) and subserosal invasive front (hazard ratio=2.9, P=0.0033) were independent prognostic factors. In contrast, the grades of LN-5gamma2 expression in the central area and rolled edge did not have a significant impact on patient prognosis. Analysis using area-specific four-point TMAs clearly demonstrated that LN-5gamma2 expression in the invasive front largely influences the degree of clinical aggressiveness of CRC and its tendency to metastasize.
层粘连蛋白-5γ2链（LN-5γ2）是多种癌症侵袭的标志物。我们的目的是通过组织微阵列（TMA）研究LN-5γ2在个体结直肠癌（CRC）不同区域表达的预后意义，并明确预后评估的最佳区域。我们使用从120例患者切除的pT3原发性CRC的福尔马林固定石蜡包埋组织块，构建了取自每个肿瘤黏膜下浸润前沿、浆膜下浸润前沿、中心区域和卷边的组织芯标本的TMA块。使用这些四点TMA组，通过免疫组织化学方法检测细胞质LN-5γ2的表达，并评估LN-5γ2表达的区域特异性预后意义。数据显示，120例CRC中分别有35%、30%、15%和10%在黏膜下浸润前沿、浆膜下浸润前沿、中心区域和卷边显示高级别LN-5γ2表达。黏膜下浸润前沿和浆膜下浸润前沿高、低级别LN-5γ2组的疾病特异性生存曲线有显著差异或边缘差异（黏膜下浸润前沿5年生存率分别为54%和78%（P = 0.030），浆膜下浸润前沿为58%和75%（P = 0.055））。多变量分析显示，黏膜下浸润前沿（风险比=2.0，P = 0.047）和浆膜下浸润前沿（风险比=2.9，P = 0.0033）的LN-5γ2表达级别是独立的预后因素。相比之下，中心区域和卷边的LN-5γ2表达级别对患者预后没有显著影响。使用区域特异性四点TMA进行的分析清楚地表明，浸润前沿的LN-5γ2表达在很大程度上影响CRC的临床侵袭程度及其转移倾向。
