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Prognostic Significance and Molecular Associations of Tumor Growth Pattern in Colorectal Cancer

  • Gastrointestinal Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Infiltrative growth pattern at the tumor margin has been associated with shorter patient survival. However, little is known about the prognostic significance of tumor growth pattern, independent of tumoral molecular alterations and other histologic features.

Methods

Utilizing a database of 1139 colon and rectal cancer patients in two prospective cohort studies, histologic features including tumor growth pattern, tumor differentiation, lymphocytic reaction, mucinous component, and signet ring cell component were recorded by a single pathologist. Cox proportional hazard model was used to compute mortality hazard ratio, adjusting for clinical, pathologic, and tumor molecular features, including microsatellite instability, the CpG island methylator phenotype, long interspersed nucleotide element 1 (LINE-1) methylation, and KRAS, BRAF, and PIK3CA mutations.

Results

Among 1139 colorectal cancers, we observed expansile growth pattern in 372 tumors (33%), intermediate growth pattern in 610 tumors (54%), and infiltrative growth pattern in 157 tumors (14%). Compared to patients with expansile growth pattern, those with infiltrative growth pattern experienced shorter cancer-specific survival (log rank P < 0.0001; multivariate hazard ratio 1.74; 95% confidence interval 1.22–2.47) and overall survival (log rank P < 0.0001; multivariate hazard ratio 1.78; 95% confidence interval 1.33–2.39). The prognostic association of infiltrative growth pattern was confined to patients with stage I–III disease (P interaction with stage = 0.0001).

Conclusions

Infiltrative growth pattern was associated with worse prognosis among stage I–III colorectal cancer patients, independent of other clinical, pathologic, and molecular characteristics.

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Acknowledgment

We thank the participants and staff of the Nurses’ Health Study and the Health Professionals Follow-up Study, for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. This work was supported by U.S. National Institute of Health (NIH) grants P01 CA87969 (to S. Hankinson), P01 CA55075 (to W. Willett), P50 CA127003 (to C.S.F.), and R01 CA151993 (to S.O.) and by grants from the Bennett Family Fund and the Entertainment Industry Foundation through National Colorectal Cancer Research Alliance. T.M. was supported by a fellowship grant from the Japan Society for Promotion of Science. The content is solely the responsibility of the authors and does not necessarily represent the official views of NCI or NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Authors and Affiliations

  1. Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA

    Teppei Morikawa MD, PhD, Aya Kuchiba PhD, Zhi Rong Qian MD, PhD, Mai Yamauchi PhD, Yu Imamura MD, PhD, Xiaoyun Liao MD, PhD, Reiko Nishihara PhD, Jeffrey A. Meyerhardt MD, MPH, Charles S. Fuchs MD, MPH & Shuji Ogino MD, PhD, MS

  2. Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA

    Mari Mino-Kenudson MD

  3. Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

    Jason L. Hornick MD, PhD & Shuji Ogino MD, PhD, MS

  4. Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

    Charles S. Fuchs MD, MPH

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  1. Teppei Morikawa MD, PhD
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  2. Aya Kuchiba PhD
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  3. Zhi Rong Qian MD, PhD
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  4. Mari Mino-Kenudson MD
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  9. Reiko Nishihara PhD
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  12. Shuji Ogino MD, PhD, MS
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Corresponding author

Correspondence to Teppei Morikawa MD, PhD.

Additional information

The first three authors contributed equally to this study.

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Morikawa, T., Kuchiba, A., Qian, Z.R. et al. Prognostic Significance and Molecular Associations of Tumor Growth Pattern in Colorectal Cancer. Ann Surg Oncol 19, 1944–1953 (2012). https://doi.org/10.1245/s10434-011-2174-5

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  • DOI: https://doi.org/10.1245/s10434-011-2174-5

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