Comprehensive characterization of micropapillary colorectal adenocarcinoma

IF 5.6 2区医学 Q1 ONCOLOGY

The Journal of Pathology Pub Date : 2025-02-07 DOI:10.1002/path.6392

Ville K Äijälä, Jouni Härkönen, Tuomo Mantere, Hanna Elomaa, Päivi Sirniö, Vesa-Matti Pohjanen, Onni Sirkiä, Henna Karjalainen, Meeri Kastinen, Vilja V Tapiainen, Sara A Väyrynen, Petri Pölönen, Maarit Ahtiainen, Olli Helminen, Erkki-Ville Wirta, Jukka Rintala, Sanna Meriläinen, Juha Saarnio, Tero Rautio, Katri Pylkäs, Toni T Seppälä, Jan Böhm, Jukka-Pekka Mecklin, Anne Tuomisto, Markus J Mäkinen, Juha P Väyrynen

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Abstract

Micropapillary colorectal adenocarcinoma is a morphologic subtype of colorectal cancer (CRC) with insufficiently characterized prognostic significance and biological features. We analyzed the histopathological, immunological, and prognostic features of micropapillary adenocarcinoma in two independent CRC cohorts (N = 1,876). We found that micropapillary adenocarcinomas accounted for 4.9% and 6.4% of CRCs in the two cohorts. A micropapillary growth pattern was associated with advanced stage and lymphovascular invasion (p < 0.001), but also with shorter overall survival independent of these factors and other prognostic parameters (Cohort 1: hazard ratio [HR] 1.76, 95% confidence interval [CI] 1.08–2.87; Cohort 2: HR 1.47, 95% CI 1.08–2.00). Multiplex immunohistochemistry and machine learning-assisted image analysis showed that the micropapillary growth pattern was associated with decreased CD3⁺ T-cell and CD14⁺HLA-DR⁺ monocytic cell densities. Molecular features of micropapillary adenocarcinoma were studied using bioinformatic analyses in The Cancer Genome Atlas (TCGA) cohort (N = 629) and validated with optical genome mapping and immunohistochemistry. These analyses revealed that micropapillary adenocarcinomas frequently present with chromosome region 8q24 copy number gain, TP53 mutation, and overexpression of UPK2, MUC16, and epithelial-mesenchymal transition involved genes, such as L1CAM. These results indicate that micropapillary colorectal adenocarcinoma is an aggressive morphologic subtype of CRC characterized by shorter overall survival, decreased antitumorigenic immune response, and unique molecular features. Our findings support the classification of micropapillary adenocarcinoma as a distinct, high-risk subtype of CRC, which should be systematically evaluated in patient care. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

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结直肠微乳头状腺癌的综合表征。

微乳头状结直肠腺癌是结直肠癌（CRC）的一种形态学亚型，其预后意义和生物学特征尚未充分表征。我们分析了两个独立CRC队列（N = 1876）中微乳头状腺癌的组织病理学、免疫学和预后特征。我们发现在两个队列中，微乳头状腺癌分别占crc的4.9%和6.4%。微乳头状生长模式与晚期和淋巴血管侵袭（p + t细胞和CD14+HLA-DR+单核细胞密度）有关。在癌症基因组图谱（TCGA）队列（N = 629）中使用生物信息学分析研究了微乳头状腺癌的分子特征，并通过光学基因组定位和免疫组织化学进行了验证。这些分析表明，微乳头状腺癌经常表现为染色体区域8q24拷贝数增加、TP53突变、UPK2、MUC16和上皮间质转化相关基因（如L1CAM）的过表达。这些结果表明，微乳头状结直肠腺癌是CRC的一种侵袭性形态亚型，其特点是总生存期较短，抗肿瘤免疫反应降低，并且具有独特的分子特征。我们的研究结果支持将微乳头状腺癌分类为CRC的一种独特的高风险亚型，应在患者护理中进行系统评估。©2025作者。《病理学杂志》由John Wiley & Sons Ltd代表大不列颠和爱尔兰病理学会出版。

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来源期刊

The Journal of Pathology 医学-病理学

CiteScore

14.10

自引率

1.40%

发文量

144

审稿时长

3-8 weeks

期刊介绍： The Journal of Pathology aims to serve as a translational bridge between basic biomedical science and clinical medicine with particular emphasis on, but not restricted to, tissue based studies. The main interests of the Journal lie in publishing studies that further our understanding the pathophysiological and pathogenetic mechanisms of human disease. The Journal of Pathology welcomes investigative studies on human tissues, in vitro and in vivo experimental studies, and investigations based on animal models with a clear relevance to human disease, including transgenic systems. As well as original research papers, the Journal seeks to provide rapid publication in a variety of other formats, including editorials, review articles, commentaries and perspectives and other features, both contributed and solicited.