MUC4 expression is a novel prognostic factor in patients with invasive ductal carcinoma of the pancreas - PubMed (original) (raw)
doi: 10.1136/jcp.2004.023572.
M Goto, M Horinouchi, S Tamada, K Nagata, T Hamada, M Osako, S Takao, S K Batra, T Aikou, K Imai, S Yonezawa
Affiliations
- PMID: 16049287
- PMCID: PMC1770880
- DOI: 10.1136/jcp.2004.023572
MUC4 expression is a novel prognostic factor in patients with invasive ductal carcinoma of the pancreas
M Saitou et al. J Clin Pathol. 2005 Aug.
Abstract
Background: Many patients with invasive ductal carcinoma of the pancreas (IDC) have a poor outcome. MUC4 expression has been implicated as a marker for diagnosis and progression of IDC, but there are no studies of the relation between MUC4 expression and patient prognosis in IDC.
Aims: To investigate the prognostic significance of MUC4 expression in IDC.
Methods: The expression profiles of MUC4, ErbB2, p27, and MUC1 were investigated in IDC tissues from 135 patients by means of immunohistochemistry.
Results: MUC4 was expressed in 43 of the 135 patients with IDC (31.9%). The survival of 21 patients with high MUC4 expression (>20% of neoplastic cells stained) was significantly worse than that of the 114 patients with low MUC4 expression (<20% of neoplastic cells stained) (p = 0.0043). Univariate analysis showed that high MUC4 expression (p = 0.0061), large primary tumour status (>T2) (p = 0.0436), distant metastasis (p = 0.0383), lymphatic invasion (p = 0.0243), and surgical margins (p = 0.0333) were significant risk factors affecting the outcome of patients with IDC. Backward stepwise multivariate analysis showed that MUC4 expression (p = 0.0121), lymph node metastasis (p = 0.0245), and lymphatic invasion (p = 0.0239) were significant independent risk factors. ErbB2, p27, and MUC1 were not independent risk factors.
Conclusions: This study shows that MUC4 expression in IDC is a new independent factor for poor prognosis and predicts the outcome of patients with IDC.
Figures
Figure 1
Immunohistochemical staining of (A, B) MUC4, (C) ErbB2, (D) p27, and (E) MUC1 in invasive ductal carcinoma of the pancreas. MUC4 was expressed in the carcinoma tissue (A, left), but not in the normal pancreas tissue (A, right) (original magnification, ×40). MUC4 expression was seen in the cytoplasm and/or membrane of the carcinoma cells (B, original magnification, ×160). ErbB2 was expressed in the membrane and/or cytoplasm of the carcinoma cells (C, original magnification, ×160). p27 expression was seen in the nuclei of the carcinoma cells (D, original magnification, ×160). MUC1 was expressed in the membrane and/or cytoplasm of the carcinoma cells (E, original magnification, ×160).
Figure 2
Correlation between MUC4 expression and cumulative survival rate in 135 patients with invasive ductal carcinoma, as determined by the Kaplan–Meier method. The survival of patients with high MUC4 expression was worse than those with low MUC4 expression (p = 0.0043). The open circles represent those patients who were alive at the last follow up.
Figure 3
Combined evaluation of MUC4 and p27 expression. Patients with both high MUC4 and p27 expression had the worst outcome. In contrast, patients with both low MUC4 and p27 expression had the best outcome. A significant difference for survival was found between the two groups (p < 0.0001). The open circles represent those patients who were alive at the last follow up.
Similar articles
- MUC4 is a novel prognostic factor of extrahepatic bile duct carcinoma.
Tamada S, Shibahara H, Higashi M, Goto M, Batra SK, Imai K, Yonezawa S. Tamada S, et al. Clin Cancer Res. 2006 Jul 15;12(14 Pt 1):4257-64. doi: 10.1158/1078-0432.CCR-05-2814. Clin Cancer Res. 2006. PMID: 16857800 - Aberrant methylation of MUC1 and MUC4 promoters are potential prognostic biomarkers for pancreatic ductal adenocarcinomas.
Yokoyama S, Higashi M, Kitamoto S, Oeldorf M, Knippschild U, Kornmann M, Maemura K, Kurahara H, Wiest E, Hamada T, Kitazono I, Goto Y, Tasaki T, Hiraki T, Hatanaka K, Mataki Y, Taguchi H, Hashimoto S, Batra SK, Tanimoto A, Yonezawa S, Hollingsworth MA. Yokoyama S, et al. Oncotarget. 2016 Jul 5;7(27):42553-42565. doi: 10.18632/oncotarget.9924. Oncotarget. 2016. PMID: 27283771 Free PMC article. - MUC4 expression correlates with poor prognosis in small-sized lung adenocarcinoma.
Tsutsumida H, Goto M, Kitajima S, Kubota I, Hirotsu Y, Wakimoto J, Batra SK, Imai K, Yonezawa S. Tsutsumida H, et al. Lung Cancer. 2007 Feb;55(2):195-203. doi: 10.1016/j.lungcan.2006.10.013. Epub 2006 Nov 28. Lung Cancer. 2007. PMID: 17126950 - Significance of mucin expression in pancreatobiliary neoplasms.
Yonezawa S, Higashi M, Yamada N, Yokoyama S, Goto M. Yonezawa S, et al. J Hepatobiliary Pancreat Sci. 2010 Mar;17(2):108-24. doi: 10.1007/s00534-009-0174-7. Epub 2009 Sep 29. J Hepatobiliary Pancreat Sci. 2010. PMID: 19787286 Review. - MUC4 mucin- a therapeutic target for pancreatic ductal adenocarcinoma.
Gautam SK, Kumar S, Cannon A, Hall B, Bhatia R, Nasser MW, Mahapatra S, Batra SK, Jain M. Gautam SK, et al. Expert Opin Ther Targets. 2017 Jul;21(7):657-669. doi: 10.1080/14728222.2017.1323880. Epub 2017 May 29. Expert Opin Ther Targets. 2017. PMID: 28460571 Free PMC article. Review.
Cited by
- Pancreatic Adenocarcinoma: Imaging Modalities and the Role of Artificial Intelligence in Analyzing CT and MRI Images.
Anghel C, Grasu MC, Anghel DA, Rusu-Munteanu GI, Dumitru RL, Lupescu IG. Anghel C, et al. Diagnostics (Basel). 2024 Feb 16;14(4):438. doi: 10.3390/diagnostics14040438. Diagnostics (Basel). 2024. PMID: 38396476 Free PMC article. Review. - Mucins as Potential Biomarkers for Early Detection of Cancer.
Gautam SK, Khan P, Natarajan G, Atri P, Aithal A, Ganti AK, Batra SK, Nasser MW, Jain M. Gautam SK, et al. Cancers (Basel). 2023 Mar 7;15(6):1640. doi: 10.3390/cancers15061640. Cancers (Basel). 2023. PMID: 36980526 Free PMC article. Review. - Radiomics models based on multi-sequence MRI for preoperative evaluation of MUC4 status in pancreatic ductal adenocarcinoma: a preliminary study.
Deng Y, Li Y, Wu JL, Zhou T, Tang MY, Chen Y, Zuo HD, Tang W, Chen TW, Zhang XM. Deng Y, et al. Quant Imaging Med Surg. 2022 Nov;12(11):5129-5139. doi: 10.21037/qims-22-112. Quant Imaging Med Surg. 2022. PMID: 36330180 Free PMC article. - Association of mucin family members with prognostic significance in pancreatic cancer patients: A meta-analysis.
Xu W, Zhang M, Liu L, Yin M, Xu C, Weng Z. Xu W, et al. PLoS One. 2022 Jun 16;17(6):e0269612. doi: 10.1371/journal.pone.0269612. eCollection 2022. PLoS One. 2022. PMID: 35709153 Free PMC article. - Depletion of transmembrane mucin 4 (Muc4) alters intestinal homeostasis in a genetically engineered mouse model of colorectal cancer.
Pothuraju R, Pai P, Chaudhary S, Siddiqui JA, Cox JL, Kaur S, Rachagani S, Roy HK, Bouvet M, Batra SK. Pothuraju R, et al. Aging (Albany NY). 2022 Mar 7;14(5):2025-2046. doi: 10.18632/aging.203935. Epub 2022 Mar 7. Aging (Albany NY). 2022. PMID: 35255004 Free PMC article.
References
- Matsuno S, Egawa S, Fukuyama S, et al. Pancreatic cancer registry in Japan: 20 years of experience. Pancreas 2004;28:219–30. - PubMed
- Isaji S, Kawarada Y, Uemoto S. Classification of pancreatic cancer: comparison of Japanese and UICC classifications. Pancreas 2004;28:231–4. - PubMed
- Egawa S, Takeda K, Fukuyama S, et al. Clinicopathological aspects of small pancreatic cancer. Pancreas 2004;28:235–40. - PubMed
- Yonezawa S, Sato E. Expression of mucin antigens in human cancers and its relationship with malignancy potential. Pathol Int 1997;47:813–30. - PubMed
- D’Cruz OJ, Dunn TS, Pichan P, et al. Antigenic cross-reactivity of human tracheal mucin with human sperm and trophoblasts correlates with the expression of mucin 8 gene messenger ribonucleic acid in reproductive tract tissues. Fertil Steril 1996;66:316–26. - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Molecular Biology Databases
Research Materials
Miscellaneous