Morphofunctional malignancy grading is a valuable prognostic factor for colorectal cancer

CONTEXT: Novel strategies are needed to identify more efficient biomarkers to accurately diagnose prognose and improve the treatment outcome of colorectal cancer. OBJECTIVES: To analyze the functional and morphological features of colorectal cancer to identify the neoplastic patterns that affect patient survival. METHODS: Forty-five patients with colorectal cancer were followed for a minimum of 3 years. Blood levels of carcinoembryonic antigen (CEA) were measured by chemiluminescence and immunohistochemical analysis of tissue expression followed by computer-assisted image processing. Tumors were assigned to three morphofunctional classes. The morphofunctional classification was based on combination between histological differentiation and cell polarization. The functional characterization was based on the CEA cell polarization. The tissue polarization of CEA was classified in well-polarized, moderately polarized or nonpolarized cells. Morphofunctional staging was defined by the association between morphofunctional class (polarization and histological differentiation) and TNM by score given to each one classification. RESULTS: There was an association between increased CEA tissue expression and loss of histological differentiation (P = 0.01) or loss of polarization capacity (P = 0.03). There was a progressive increase in tissue CEA quantities in accordance with the proposed morphofunctional grading system. Plasma levels of CEA were increased in advanced tumor stages. Blood levels of CEA were increased in advanced morphofunctional stages (P = 0.001). There was a relationship between survival outcome and morphofunctional staging (P = 0.005). CONCLUSION: Morphofunctional staging is a valuable prognostic factor for colorectal cancer and it correlates with plasma CEA levels.

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Colorectal cancer in Crohn’s colitis is associated with advanced tumor invasion and a poorer survival compared with ulcerative colitis: a retrospective dual-center study

International Journal of Colorectal Disease ◽

10.1007/s00384-020-03726-4 ◽

2020 ◽

Vol 36 (1) ◽

pp. 141-150

Author(s):

Leonie E. Vetter ◽

Susanne Merkel ◽

Alan Bénard ◽

Christian Krautz ◽

Maximilian Brunner ◽

...

Keyword(s):

Colorectal Cancer ◽

Ulcerative Colitis ◽

Survival Data ◽

Tumor Stage ◽

Crohn’S Colitis ◽

Crohn's Colitis ◽

Advanced Tumor ◽

Tumor Stages ◽

Bowel Diseases ◽

Inflammatory Bowel

Abstract Purpose Colorectal cancer is a well-recognized complication of inflammatory bowel diseases (IBD), such as ulcerative colitis (UC) and Crohn’s colitis (CC). In this study, we assess the clinico-pathological features and outcomes of patients with colorectal cancer from UC in comparison with CC. Methods Data of all patients with colitis-associated cancer (CAC) who underwent surgery at Erlangen or Würzburg University Clinic between 1995 and 2015 were selected. Clinical, histopathological, and survival data were analyzed retrospectively. Results Of all 88 patients with CAC, 20 patients had Crohn’s colitis and 68 patients had ulcerative colitis. We observed a young median age at tumor diagnosis (49.5 years UC; 45.5 years CC, p = 0.208) in both diseases and a long median disease duration before CAC (19 years UC; 18 years CC; p = 0.840). Patients with CC suffered more often from rectal cancer (14 (70.0%) in CC; 23 (33.8%) in UC; p = 0.005) and advanced tumor stages (8 (47.0%) pT4 in CC; 14 (25.0%) pT4/ypT4 in UC; p = 0.008). Five-year overall survival rate was 39.3% for CC and 67.1% for UC (p = 0.009 for difference between the groups). Survival did not differ significantly between UC and CC in the multivariate analysis after correction for UICC tumor stage. Conclusion CAC in CC showed advanced tumor stages associated with reduced survival compared with CAC in UC. This may be explained by less intense surveillance in patients with CC leading to delayed cancer diagnosis.

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Fecal galectin-1 as a potential marker for colorectal cancer and disease severity

Vojnosanitetski pregled ◽

10.2298/vsp171201007j ◽

2019 ◽

Vol 76 (10) ◽

pp. 1037-1044 ◽

Cited By ~ 1

Author(s):

Milan Jovanovic ◽

Nevena Gajovic ◽

Natasa Zdravkovic ◽

Marina Jovanovic ◽

Milena Jurisevic ◽

...

Keyword(s):

Colorectal Cancer ◽

Tumor Tissue ◽

Liquid Fraction ◽

Interleukin 1 ◽

Blood Vessel Invasion ◽

Enzyme Linked Immunosorbent Assay ◽

Specific Marker ◽

Histological Differentiation ◽

Potential Marker ◽

Advanced Tumor

Background/Aim. Colorectal cancer (CRC) represents one of the most common cancers worldwide. CRC is frequently diagnosed at advanced stages with poor prognosis, indicating the need for new diagnostic and prognostic markers. The aim of this study was to determine systemic and fecal values of galectin- 1 (gal-1) and ratios between gal-1 and proinflammatory cytokines: tumor necrosis factor-alpha (TNF-?), interleukin-1 beta (IL-1?) and interferon gamma (IFN-?), in the patients with CRC and the relationship with clinicopathological aspects of the disease. Methods. The blood samples and feces liquid fraction of 58 patients with CRC were analyzed. The serum and fecal levels of TNF-?, IL-1? and IFN-? and gal-1 were measured using sensitive enzyme-linked immunosorbent assay (ELISA) kits. Results. The fecal level of gal-1 was increased in the CRC patients with higher nuclear grade and poor tumor tissue differentiation. The gal-1/TNF-? ratio in the serum and feces had a higher trend in the patients with the advanced tumor-nodemetastasis (TNM) stage as well as the detectable lymphatic and blood vessel invasion. The gal-1/TNF-? and gal-1/IFN-? ratios were increased in the serum of patients with presence of lung/liver metastasis or peritoneal carcinomatosis, while the enhanced gal-1/IL-1 ratio was detected only in the serum of patients with lung metastasis. A positive correlation between the gal-1 value in feces and histological differentiation of tumor and biomarkers alpha-fetoprotein (AFP) and cancer antigen- 19-9 (CA 19-9), respectively, was also observed. The fecal values of gal-1 higher than 13,708.29 pg/g presented a highly sensitive and specific marker for histological differentiation of tumor tissue. Conclusion. We believe that the predomination of gal-1 over pro-inflammatory cytokines TNF-?, IL-1? and IFN- ? in the patients with advanced and progressive CRC may implicate on an immunomodulatory role of gal-1 in the limiting ongoing proinflammatory processes. The fecal values of gal-1 can be used as a valuable marker for the severity of CRC.

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Faculty Opinions recommendation of Primary tumor location as a prognostic factor in metastatic colorectal cancer.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725368072.793550897 ◽

2018 ◽

Author(s):

Sebastian Stintzing

Keyword(s):

Colorectal Cancer ◽

Prognostic Factor ◽

Metastatic Colorectal Cancer ◽

Primary Tumor ◽

Tumor Location ◽

Primary Tumor Location

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Clinical correlation of cadherin‐17 marker with advanced tumor stages and poor prognosis of cholangiocarcinoma

Journal of Surgical Oncology ◽

10.1002/jso.26399 ◽

2021 ◽

Author(s):

Bo‐Hao Zheng ◽

Sheng Shen ◽

Kwong‐Fai Wong ◽

Zi‐Jun Gong ◽

Wen‐Tao Sun ◽

...

Keyword(s):

Poor Prognosis ◽

Clinical Correlation ◽

Advanced Tumor ◽

Tumor Stages

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Distribution of tumor-infiltrating-T-lymphocytes and possible tumor-escape mechanisms avoiding immune cell attack in locally advanced adenocarcinomas of the esophagus

Clinical & Translational Oncology ◽

10.1007/s12094-021-02556-2 ◽

2021 ◽

Author(s):

M. Schoemmel ◽

◽

H. Loeser ◽

M. Kraemer ◽

S. Wagener-Ryczek ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Immune Cell ◽

Locally Advanced ◽

Tumor Escape ◽

Inflammatory Microenvironment ◽

Advanced Tumor ◽

Tumor Stages ◽

Tumor Center ◽

Class 1

Abstract Introduction The inflammatory microenvironment has emerged as one of the focuses of cancer research. Little is known about the immune environment in esophageal adenocarcinoma (EAC) and possible tumor-escape mechanisms to avoid immune cell attack. Patients and methods We measured T cell inflammation (CD3, CD8) in the microenvironment using a standardized software-based evaluation algorithm considering different predefined tumor areas as well as expression of MHC class 1 and PD-L1 on 75 analyzable primarily resected and locally advanced (≥ pT2) EACs. We correlated these findings statistically with clinical data. Results Patients with high amounts of T cell infiltration in their tumor center showed a significant survival benefit of 41.4 months compared to 16.3 months in T cell poor tumors (p = 0.025), although CD3 fails to serve as an independent prognostic marker in multivariate analysis. For the invasion zone, a correlation between number of T-cells and overall survival was not detectable. Loss of MHC1 protein expression on tumor cells was seen in 32% and PD-L1 expression using the combined positive score (CPS) in 21.2%. Most likely due to small numbers of cases, both markers are not prognostically relevant, even though PD-L1 expression correlates with advanced tumor stages. Discussion Our analyses reveal an outstanding, though not statistically independent, prognostic relevance of T-cell-rich inflammation in our group of EACs, in particular driven by the tumor center. For the first time, we describe that the inner part of the invasion zone in EACs shows significantly fewer T-cells than other tumor segments and is prognostically irrelevant. We also demonstrate that the loss of antigen presenting ability via MHC1 downregulation by the carcinoma cells is a common escape mechanism in EACs. Future work will need to show whether tumors with MHC class 1 loss respond less well to immunotherapy.

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Colorectal carcinomas with KRAS codon 12 mutation are associated with more advanced tumor stages

BMC Cancer ◽

10.1186/s12885-015-1345-3 ◽

2015 ◽

Vol 15 (1) ◽

Cited By ~ 32

Author(s):

Wenbin Li ◽

Tian Qiu ◽

Wenxue Zhi ◽

Susheng Shi ◽

Shuangmei Zou ◽

...

Keyword(s):

Colorectal Carcinomas ◽

Advanced Tumor ◽

Tumor Stages ◽

Kras Codon

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Karyopherin alpha 2 expression is a novel diagnostic and prognostic factor for colorectal cancer

Oncology Letters ◽

10.3892/ol.2017.5579 ◽

2017 ◽

Vol 13 (3) ◽

pp. 1194-1200 ◽

Cited By ~ 8

Author(s):

Lei Yu ◽

Guiyu Wang ◽

Qian Zhang ◽

Li Gao ◽

Rui Huang ◽

...

Keyword(s):

Colorectal Cancer ◽

Prognostic Factor

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PDGF-BB is a Novel Prognostic Factor in Colorectal Cancer

Annals of Surgical Oncology ◽

10.1245/s10434-008-9943-9 ◽

2008 ◽

Vol 15 (8) ◽

pp. 2129-2136 ◽

Cited By ~ 37

Author(s):

Yoshito Nakamura ◽

Fumiaki Tanaka ◽

Yasuji Yoshikawa ◽

Koshi Mimori ◽

Hiroshi Inoue ◽

...

Keyword(s):

Colorectal Cancer ◽

Prognostic Factor

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TREM1 fosters an immunosuppressive tumor microenvironment in papillary thyroid cancer

Endocrine Related Cancer ◽

10.1530/erc-21-0297 ◽

2021 ◽

Author(s):

Yang Zhao ◽

Cangang Zhang ◽

Yanan Zhu ◽

Xi Ding ◽

Yikun Zhou ◽

...

Keyword(s):

T Cells ◽

Thyroid Cancer ◽

Papillary Thyroid Cancer ◽

Molecular Mechanisms ◽

Methylation Status ◽

Disease Free Survival ◽

Papillary Thyroid ◽

Advanced Tumor ◽

Tumor Stages ◽

Immunosuppressive Microenvironment

The immunosuppressive microenvironment is associated with poor prognosis in papillary thyroid cancer (PTC); however, the molecular mechanisms involved are unknown. Among triggering receptor expressed on myeloid cell (TREM) family, we found that TREM1 expression in PTC was significantly higher than that in normal tissues. TREM1 overexpression was associated with BRAFV600E profiles and advanced tumor stages. Furthermore, TREM1 mRNA expression was negatively correlated with promoter methylation status. Specifically, hypomethylation of CpG site cg06196379 in the TREM1 promoter was related with poor patient disease free survival (DFS) and a high PTC recurrence rate. Mechanistically, TREM1 was mainly expressed in malignant epithelial cells but not macrophages in PTC by single-cell analysis. PTC tissues with high TREM1 levels had enhanced infiltration of regulatory T cells (Tregs) and decreased infiltration of CD8+ T cells. Our study confirms that hypomethylation-mediated overexpression of TREM1 in PTC cells promotes an immunosuppressive microenvironment by enhancing Treg infiltration. We recommend the future use of therapeutic strategy targeting TREM1 for the treatment of PTC.

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