Väyrynen Sara A, Väyrynen Juha P, Klintrup Kai, Mäkelä Jyrki, Karttunen Tuomo J, Tuomisto Anne, Mäkinen Markus J
Department of Pathology, Cancer and Translational Medicine Research Unit, University of Oulu, POB 5000, Oulu 90014, Finland.
Department of Pathology, Oulu University Hospital and Medical Research Center Oulu, POB 21, Oulu 90029, Finland.
Br J Cancer. 2016 Jun 14;114(12):1334-42. doi: 10.1038/bjc.2016.128. Epub 2016 May 19.
The disease outcome in colorectal cancer (CRC) can vary in a wide range within the same tumour stage. The aim of this study was to clarify the prognostic value and the determinants of tumour necrosis in CRC.
The areal proportion (%) of tumour tissue showing coagulative necrosis was evaluated in a cohort of 147 CRC patients and correlated with basic clinicopathological characteristics, microvascular density (MVD), cell proliferation rate, KRAS and BRAF mutations, and survival. To validate the prognostic significance of tumour necrosis, an independent cohort of 418 CRC patients was analysed.
Tumour necrosis positively correlated with tumour stage (P=8.5E-4)-especially with T class (4.0E-6)-and inversely correlated with serrated histology (P=0.014), but did not significantly associate with cell proliferation rate, MVD, and KRAS or BRAF mutation. Abundant (10% or more) tumour necrosis associated with worse disease-free survival independent of stage and other biological or clinicopathological characteristics in both cohorts, and the adverse effect was directly related to its extent. High CD105 MVD was also a stage independent marker for worse disease-free survival.
Tumour necrosis percentage is a relevant histomorphological prognostic indicator in CRC. More studies are needed to disclose the mechanisms of tumour necrosis.
在相同肿瘤分期内,结直肠癌(CRC)的疾病转归差异很大。本研究旨在阐明CRC中肿瘤坏死的预后价值及其决定因素。
在147例CRC患者队列中评估显示凝固性坏死的肿瘤组织面积比例(%),并将其与基本临床病理特征、微血管密度(MVD)、细胞增殖率、KRAS和BRAF突变以及生存率相关联。为验证肿瘤坏死的预后意义,分析了418例CRC患者的独立队列。
肿瘤坏死与肿瘤分期呈正相关(P = 8.5E - 4),尤其是与T分类呈正相关(4.0E - 6),与锯齿状组织学呈负相关(P = 0.014),但与细胞增殖率、MVD以及KRAS或BRAF突变无显著关联。在两个队列中,大量(10%或更多)肿瘤坏死与较差的无病生存率相关,且与分期及其他生物学或临床病理特征无关,其不良影响与其程度直接相关。高CD105 MVD也是无病生存率较差的分期独立标志物。
肿瘤坏死百分比是CRC中一个相关的组织形态学预后指标。需要更多研究来揭示肿瘤坏死的机制。