J Pathol Transl Med.  2015 Mar;49(2):118-128. 10.4132/jptm.2015.02.05.

Pathologic Factors Associated with Prognosis after Adjuvant Chemotherapy in Stage II/III Microsatellite-Unstable Colorectal Cancers

• Kim JH
• Bae JM
• Oh HJ
• Lee HS
• Kang GH

• KMID: 2381366
• DOI: http://doi.org/10.4132/jptm.2015.02.05

Abstract

BACKGROUND
Although there are controversies regarding the benefit of fluoropyrimidine-based adjuvant chemotherapy in patients with microsatellite instability-high (MSI-H) colorectal cancer (CRC), the pathologic features affecting postchemotherapeutic prognosis in these patients have not been fully identified yet.
METHODS
A total of 26 histopathologic and immunohistochemical factors were comprehensively evaluated in 125 stage II or III MSI-H CRC patients who underwent curative resection followed by fluoropyrimidine-based adjuvant chemotherapy. We statistically analyzed the associations of these factors with disease-free survival (DFS).
RESULTS
Using a Kaplan- Meier analysis with log-rank test, we determined that ulceroinfiltrative gross type (p=.003), pT4 (p<.001), pN2 (p=.002), perineural invasion (p=.001), absence of peritumoral lymphoid reaction (p=.041), signet ring cell component (p=.006), and cribriform comedo component (p=.004) were significantly associated with worse DFS in patients receiving oxaliplatin-based adjuvant chemotherapy (n=45). By contrast, pT4 (p<.001) and tumor budding-positivity (p=.032) were significant predictors of poor survival in patients receiving non-oxaliplatin-based adjuvant chemotherapy (n=80). In Cox proportional hazards regression model-based univariate and multivariate analyses, pT category (pT1-3 vs pT4) was the only significant prognostic factor in patients receiving non-oxaliplatin-based adjuvant chemotherapy, whereas pT category, signet ring cell histology and cribriform comedo histology remained independent prognostic factors in patients receiving oxaliplatin-based adjuvant chemotherapy.
CONCLUSIONS
pT4 status is the most significant pathologic determinant of poor outcome after fluoropyrimidine-based adjuvant chemotherapy in patients with stage II/III MSI-H CRC.

Keyword

Chemotherapy, adjuvant; Colorectal neoplasms; Pathology; Microsatellite instability; Prognosis

MeSH Terms

Cellular Structures
Chemotherapy, Adjuvant*
Colorectal Neoplasms*
Disease-Free Survival
Humans
Microsatellite Instability
Microsatellite Repeats
Multivariate Analysis
Pathology
Prognosis*

Figure

• 

  Fig. 1. Histopathologic features in microsatellite instability–high colorectal cancers. (A) A case determined to be tumor budding–positive (buds ≥5). (B) A case classified as mucinous adenocarcinoma. (C) A case classified as signet ring cell carcinoma. (D) A case classified as medullary carcinoma. (E) A case showing a serrated tumor component. (F) A case showing a cribriform comedo-type tumor component.

• 

  Fig. 2. Immunohistochemical expression of wild-type HSP110 (HSP110wt) and thymidylate synthase (TS) in microsatellite instability–high colorectal cancers. (A) A case showing high-level expression of HSP110wt (score 3+). (B) A case showing HSP110wt-negativity (score 0). (C) A case showing high-level expression of TS (score 3+). (D) A case showing low-level expression of TS (score 0).

• 

  Fig. 3. Kaplan-Meier survival analyses of microsatellite instability–high colorectal cancer patients receiving oxaliplatin-based chemotherapy (n=45). (A-G) The disease-free survival of patients differed significantly according to gross tumor type (A), pT category (B), pN category (C), perineural invasion (D), peritumoral lymphoid reaction (E), signet ring cell component (F), and cribriform comedo component (G). (H) Note the absence of death or tumor recurrence in patients with wild-type HSP110 (HSP110wt)-negative tumors.

• 

  Fig. 4. Kaplan-Meier survival analyses of microsatellite instability-high colorectal cancer patients receiving non-oxaliplatin–based chemotherapy (n=80). (A, B) The disease-free survival of patients differed significantly according to the pT category (A) and tumor budding (B). (C) Note the absence of death or tumor recurrence in patients with wild-type HSP110 (HSP110wt)-negative tumors.

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