Open Access

Identification of colorectal cancers with defective DNA damage repair by immunohistochemical profiling of mismatch repair proteins, CDX2 and BRCA1

  • Authors:
    • Savitha Rajarajan
    • Anupama C.Ε
    • Betsy Jose
    • Marjorie Correa
    • Sagar Sengupta
    • Jyothi S. Prabhu
  • View Affiliations

  • Published online on: September 1, 2020     https://doi.org/10.3892/mco.2020.2128
  • Article Number: 57
  • Copyright: © Rajarajan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Colorectal cancer (CRC) is a complex disease as shown by consensus classification. The present study attempted to identify subtypes with known prognostic markers for better clinical management. A total of 72 CRC tumors were examined for the expression of mismatch repair (MMR) proteins, along with caudal‑type homeobox protein 2 (CDX2) and BRCA1, by immunohistochemistry. Tumors were assigned based on the presence or loss of MMR proteins as proficient or deficient. Correlations were examined with CDX2 and BRCA1 along with clinico‑pathological features. Expressional pattern of microRNAs (miRs/miRNAs), such as miR‑183‑96‑182, known to be associated with defective DNA damage repair were evaluated by reverse transcription‑quantitative PCR. A total of 22% of the CRC tumors were assigned as deficient in mismatch repair. 71% of the tumors expressed CDX2 while only 21% had nuclear expression of BRCA1. Loss of CDX2 protein was higher in the deficient subtype compared with the proficient subtype. A total of 14% of the tumors had dual loss of MMR and BRCA1 proteins and showed aggressive clinical features in addition to elevated expression of DNA damage repair microRNAs. The present study shows the presence of a small proportion of colorectal tumors with dual loss of key proteins involved in DNA damage repair which may be amenable to specific therapy. The implication of the present observations warrants investigation in a larger patient cohort with prognostic information.
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November-2020
Volume 13 Issue 5

Print ISSN: 2049-9450
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Spandidos Publications style
Rajarajan S, C.Ε A, Jose B, Correa M, Sengupta S and Prabhu JS: Identification of colorectal cancers with defective DNA damage repair by immunohistochemical profiling of mismatch repair proteins, CDX2 and BRCA1. Mol Clin Oncol 13: 57, 2020
APA
Rajarajan, S., C.Ε, A., Jose, B., Correa, M., Sengupta, S., & Prabhu, J.S. (2020). Identification of colorectal cancers with defective DNA damage repair by immunohistochemical profiling of mismatch repair proteins, CDX2 and BRCA1. Molecular and Clinical Oncology, 13, 57. https://doi.org/10.3892/mco.2020.2128
MLA
Rajarajan, S., C.Ε, A., Jose, B., Correa, M., Sengupta, S., Prabhu, J. S."Identification of colorectal cancers with defective DNA damage repair by immunohistochemical profiling of mismatch repair proteins, CDX2 and BRCA1". Molecular and Clinical Oncology 13.5 (2020): 57.
Chicago
Rajarajan, S., C.Ε, A., Jose, B., Correa, M., Sengupta, S., Prabhu, J. S."Identification of colorectal cancers with defective DNA damage repair by immunohistochemical profiling of mismatch repair proteins, CDX2 and BRCA1". Molecular and Clinical Oncology 13, no. 5 (2020): 57. https://doi.org/10.3892/mco.2020.2128