Sagnak Yilmaz Zeynep, Demir Kececi Sibel, Aydin Mungan Sevdegul, Saygin Ismail, Sarioglu Sulen
Department of Molecular Pathology, Dokuz Eylul University Graduate School of Health Sciences, Izmir, 35330, Turkey.
Department of Pathology, Karadeniz Technical University Faculty of Medicine, Trabzon, Turkey.
BMC Cancer. 2025 Jul 1;25(1):1100. doi: 10.1186/s12885-025-14487-0.
Micropapillary carcinoma (MPC) is a type of tumor that is histopathologically characterized by the presence of small papillary structures. Literature data on somatic mutations in MPCs are very limited.
One hundred fifty-nine colon resection cases diagnosed with adenocarcinoma whose DNA mutations were analyzed by next-generation sequencing (NGS) were retrospectively reviewed. In 10 cases, the MPC area exceeded 5%. Chi-square test was used to evaluate histopathologic characteristics and somatic mutations in MPCs and non-MPCs. The relationship between mutations and clinicopathological parameters in all cases was investigated.
The presence of MPC areas in carcinomas was associated with higher histologic grades (MPC: n = 6; 60% vs. non-MPC: n = 22; 14.8%), more advanced pathologic T (pT4 MPC: n = 5; 50% vs. non-MPC: n = 46; 34.6%) and N stages (pN2b MPC: n = 5; 50% vs. non-MPC: n = 26; 19.5%) and more frequent tumor deposits (MPC: n = 7; 87.5% vs. non-MPC: n = 44; 46.8%), lymphovascular invasion (MPC: n = 8; 80% vs. non-MPC: n = 83; 55.7%), and perineural invasion (MPC: n = 7; 70% vs. non-MPC: n = 42; 28.2%). A significant difference was found between MPCs and non-MPCs in terms of histological grade (p = 0.002) and perineural invasion (p = 0.01). TP53, KRAS, and PIK3CA genes were the most frequently mutated genes in both MPCs and non-MPCs (TP53 MPC: n = 6; 100% vs. non-MPC: n = 72; 64.9% - KRAS MPC: n = 4; 40% vs. non-MPC: n = 66; 44.3% - PIK3CA MPC: n = 2; 20% vs. non-MPC: n = 32; 21.5%). There was no statistically significant difference in somatic mutations between the groups (TP53: p = 0.177, KRAS: p = 1.000, PIK3CA: p = 1.000, BRCA2: p = 0.181, ERBB2: p = 0.327, BRAF: p = 1.000, MAP2K1: p = 0.062). A significant difference was found between the TP53 mutant and TP53 wild-type groups in terms of tumor deposits (p = 0.033) and perineural invasion (p = 0.046). The male rate was significantly higher in KRAS wild-type cases (n = 69; 77.5%) compared to KRAS mutant cases (n = 38; 54.3%) (p = 0.002). The mean age, T and N staging were significantly different between PIK3CA mutant and PIK3CA wild-type cases (p = 0.01; p = 0.033; p = 0.019, respectively).
We found that MPCs had more advanced clinical stages and histological features associated with poor prognosis, such as advanced T and N stages, higher histological grade, presence of tumor deposits, lymphovascular and perineural invasion.
微乳头癌（MPC）是一种肿瘤，其组织病理学特征为存在小乳头结构。关于MPC体细胞突变的文献数据非常有限。
回顾性分析159例经下一代测序（NGS）分析DNA突变的结肠癌切除病例。其中10例MPC区域超过5%。采用卡方检验评估MPC和非MPC的组织病理学特征和体细胞突变。研究所有病例中突变与临床病理参数之间的关系。
癌组织中MPC区域的存在与更高的组织学分级相关（MPC：n = 6；60% 对比非MPC：n = 22；14.8%）、更晚期的病理T分期（pT4 MPC：n = 5；50% 对比非MPC：n = 46；34.6%）和N分期（pN2b MPC：n = 5；50% 对比非MPC：n = 26；19.5%）以及更频繁的肿瘤结节（MPC：n = 7；87.5% 对比非MPC：n = 44；46.8%）、淋巴管侵犯（MPC：n = 8；80% 对比非MPC：n = 83；55.7%）和神经周围侵犯（MPC：n = 7；70% 对比非MPC：n = 42；28.2%）。MPC和非MPC在组织学分级（p = 0.002）和神经周围侵犯（p = 0.01）方面存在显著差异。TP53、KRAS和PIK3CA基因是MPC和非MPC中最常发生突变的基因（TP53 MPC：n = 6；100% 对比非MPC：n = 72；64.9% - KRAS MPC：n = 4；40% 对比非MPC：n = 66；44.3% - PIK3CA MPC：n = 2；20% 对比非MPC：n = 32；21.5%）。两组间体细胞突变无统计学显著差异（TP53：p = 0.177，KRAS：p = 1.000，PIK3CA：p = 1.000，BRCA2：p = 0.181，ERBB2：p = 0.327，BRAF：p = 1.000，MAP2K1：p = 0.062）。TP53突变组和TP53野生型组在肿瘤结节（p = 0.033）和神经周围侵犯（p = 0.046）方面存在显著差异。KRAS野生型病例中的男性比例（n = 69；77.5%）显著高于KRAS突变病例（n = 38；54.3%）（p = 0.002）。PIK3CA突变型和PIK3CA野生型病例之间的平均年龄、T分期和N分期存在显著差异（分别为p = 0.01；p = 0.033；p = 0.019）。
我们发现MPC具有更晚期的临床分期和与预后不良相关的组织学特征，如晚期T和N分期、更高的组织学分级、肿瘤结节的存在、淋巴管和神经周围侵犯。
