J Pathol Transl Med.  2018 Nov;52(6):386-395. 10.4132/jptm.2018.10.02.

Multiplicity of Advanced T Category–Tumors Is a Risk Factor for Survival in Patients with Colorectal Carcinoma

Affiliations
  • 1Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea. ghkang@snu.ac.kr
  • 2Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.

Abstract

BACKGROUND
Previous studies on synchronous colorectal carcinoma (SCRC) have reported inconsistent results about its clinicopathologic and molecular features and prognostic significance.
METHODS
Forty-six patients with multiple advanced tumors (T2 or higher category) who did not receive neoadjuvant chemotherapy and/or radiotherapy and who are not associated with familial adenomatous polyposis were selected and 99 tumors from them were subjected to clinicopathologic and molecular analysis. Ninety-two cases of solitary colorectal carcinoma (CRC) were selected as a control considering the distributions of types of surgeries performed on patients with SCRC and T categories of individual tumors from SCRC.
RESULTS
SCRC with multiple advanced tumors was significantly associated with more frequent nodal metastasis (p = .003) and distant metastasis (p = .001) than solitary CRC. KRAS mutation, microsatellite instability, and CpG island methylator phenotype statuses were not different between SCRC and solitary CRC groups. In univariate survival analysis, overall and recurrence-free survival were significantly lower in patients with SCRC than in patients with solitary CRC, even after adjusting for the extensiveness of surgical procedure, adjuvant chemotherapy, or staging. Multivariate Cox regression analysis revealed that tumor multiplicity was an independent prognostic factor for overall survival (hazard ratio, 4.618; 95% confidence interval, 2.126 to 10.030; p < .001), but not for recurrence-free survival (p = .151).
CONCLUSIONS
Findings suggested that multiplicity of advanced T category-tumors might be associated with an increased risk of nodal metastasis and a risk factor for poor survival, which raises a concern about the guideline of American Joint Committee on Cancer's tumor-node-metastasis staging that T staging of an index tumor determines T staging of SCRC.

Keyword

Synchronous colorectal carcinoma; Multiple colorectal carcinoma; Clinical outcome; T category

MeSH Terms

Adenomatous Polyposis Coli
Chemotherapy, Adjuvant
Colorectal Neoplasms*
CpG Islands
Drug Therapy
Humans
Joints
Microsatellite Instability
Neoplasm Metastasis
Phenotype
Radiotherapy
Risk Factors*

Figure

  • Fig. 1. Schematic diagram for selection of patients with synchronous colorectal cancer (CRC). FAP, familial adenomatous polyposis.

  • Fig. 2. Distribution of tumor location with specification of T category (A) and molecular features (B) for individual tumors of synchronous colorectal cancer. CIMP, CpG island methylator phenotype; CIMP-H, CIMP-high; CIMP-L, CIMP-low; CIMP-0, no methylated marker; MSI, microsatellite instability; MSI-H, MSI-high.

  • Fig. 3. Kaplan-Meier survival curves for overall survival and recurrence-free survival according to the tumor multiplicity in colorectal cancer (CRC) patients with curative surgery (n=119) (A, B), in CRC patients with curative and non-extensive surgery (85 patients with solitary CRC and 22 patients with synchronous CRC) (C, D), in CRC patients with curative and non-extensive surgery and adjuvant chemotherapy (36 patients with solitary CRC and 13 patients with synchronous CRC) (E, F), and in stage-matched CRC patients with R0 surgery and adjuvant chemotherapy (120 patients with solitary CRC and 24 patients with synchronous CRC) (G, H).


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