Expression of p27, COX-2, MLH1, and MSH2 in young patients with colon carcinoma and correlation with morphologic findings

Hum Pathol. 2013 Apr;44(4):591-7. doi: 10.1016/j.humpath.2012.07.003. Epub 2012 Oct 16.

Abstract

Despite an overall decrease in colorectal carcinoma incidence, rates of colorectal carcinoma have increased substantially in patients aged less than 40 years. Several authors have characterized morphologic features of colorectal carcinoma in young patients, with variable results. To date, there has been 1 detailed molecular and immunohistochemical study in young patients with colorectal carcinoma. We sought to expand the data regarding young patients with colorectal carcinoma by a detailed assessment of morphologic features and by assaying expression of p27, COX-2, MLH1, and MSH2, markers with prognostic or therapeutic implications in colorectal carcinoma. We searched our pathology database from 1985 to 2009 and, after exclusion of cases with insufficient data or neoadjuvant therapy, identified a study population of 23 patients aged 40 or younger, 35 patients between 41 and 49 years of age, and a control group of 83 colorectal carcinoma patients aged 50 or older. Younger patients had higher tumor grade (P = .0085), with a trend toward mucinous differentiation and lymphovascular and perineural invasion. Loss of MSH2 was more prominent in younger patients (P = .02). Loss of p27 expression was not associated with age, but was associated with higher tumor stage (P = .0278), mucinous/signet ring differentiation (P = .0185), loss of either MLH1 or MSH2 (P = .0035), and larger tumor size (P = .0019). There was a trend toward lower COX-2 expression in younger patients, with less COX-2 expression relative to previously published data. Our findings support some prior reports regarding morphologic features in colorectal carcinoma in young patients and provide novel data on expression of several markers in this population.

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Adenocarcinoma / diagnosis
  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / surgery
  • Adult
  • Age Factors
  • Biomarkers, Tumor / metabolism
  • Colorectal Neoplasms / diagnosis
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / surgery
  • Cyclooxygenase 2 / metabolism*
  • Female
  • Humans
  • Loss of Heterozygosity
  • Male
  • Middle Aged
  • MutL Protein Homolog 1
  • MutL Proteins
  • Neoplasm Proteins / metabolism*
  • Nuclear Proteins / metabolism*
  • Prognosis
  • Proliferating Cell Nuclear Antigen / metabolism*
  • Sex Factors

Substances

  • Adaptor Proteins, Signal Transducing
  • Biomarkers, Tumor
  • MLH1 protein, human
  • Neoplasm Proteins
  • Nuclear Proteins
  • PMS1 protein, human
  • Proliferating Cell Nuclear Antigen
  • p27 antigen
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • MutL Protein Homolog 1
  • MutL Proteins