Center for Experimental and Molecular Medicine, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
Department of Pathology, Radboud University Medical Centre, 6525 GA Nijmegen, The Netherlands.
Int J Mol Sci. 2022 Oct 21;23(20):12707. doi: 10.3390/ijms232012707.
The purpose of this study was to evaluate the association between four distinct histopathological features: (1) tumor infiltrating lymphocytes, (2) mucinous differentiation, (3) tumor-stroma ratio, plus (4) tumor budding and two gene expression-based classifiers—(1) consensus molecular subtypes (CMS) plus (2) colorectal cancer intrinsic subtypes (CRIS). All four histopathological features were retrospectively scored on hematoxylin and eosin sections of the most invasive part of the primary tumor in 218 stage II and III colon cancer patients from two independent cohorts (AMC-AJCC-90 and AC-ICAM). RNA-based CMS and CRIS assignments were independently obtained for all patients. Contingency tables were constructed and a χ2 test was used to test for statistical significance. Odds ratios with 95% confidence intervals were calculated. The presence of tumor infiltrating lymphocytes and a mucinous phenotype (>50% mucinous surface area) were strongly correlated with CMS1 (p < 0.001 and p = 0.008) and CRIS-A (p = 0.006 and p < 0.001). The presence of mucus (≥ 10%) was associated with CMS3: mucus was present in 64.1% of all CMS3 tumors (p < 0.001). Although a clear association between tumor-stroma ratio and CMS4 was established in this study (p = 0.006), still 32 out of 61 (52.5%) CMS4 tumors were scored as stroma-low, indicating that CMS4 tumors cannot be identified solely based on stromal content. Higher budding counts were seen in CMS4 and CRIS-B tumors (p = 0.045 and p = 0.046). No other associations of the measured parameters were seen for any of the other CRIS subtypes. Our analysis revealed clear associations between histopathologic features and CMS or CRIS subtypes. However, identification of distinct molecular subtypes solely based on histopathology proved to be infeasible. Combining both molecular and morphologic features could potentially improve patient stratification.
(1)肿瘤浸润淋巴细胞,(2)黏液分化,(3)肿瘤间质比,加上(4)肿瘤芽生,以及(1)共识分子亚型(CMS)加(2)结直肠癌固有亚型(CRIS)。在来自两个独立队列(AMC-AJCC-90 和 AC-ICAM)的 218 例 II 期和 III 期结肠癌患者的原发性肿瘤最侵袭部位的苏木精和伊红切片上,回顾性地对所有四个组织病理学特征进行评分。为所有患者独立获得基于 RNA 的 CMS 和 CRIS 分配。构建列联表并使用 χ2 检验检验统计学意义。计算优势比及其 95%置信区间。肿瘤浸润淋巴细胞和黏液表型(>50%黏液表面积)的存在与 CMS1(p<0.001 和 p=0.008)和 CRIS-A(p=0.006 和 p<0.001)密切相关。存在黏液(≥10%)与 CMS3 相关:所有 CMS3 肿瘤中均存在 64.1%的黏液(p<0.001)。尽管本研究中明确建立了肿瘤间质比与 CMS4 之间的关联(p=0.006),但在 61 个 CMS4 肿瘤中仍有 32 个(52.5%)被评为间质低,表明 CMS4 肿瘤不能仅基于间质含量来识别。CMS4 和 CRIS-B 肿瘤的芽生计数较高(p=0.045 和 p=0.046)。对于任何其他 CRIS 亚型,都没有观察到所测参数的其他关联。我们的分析揭示了组织病理学特征与 CMS 或 CRIS 亚型之间的明确关联。然而,仅基于组织病理学来识别独特的分子亚型是不可行的。将分子和形态特征相结合可能会提高患者分层的效果。