Clinicopathologic and molecular features of sporadic early-onset colorectal adenocarcinoma: an adenocarcinoma with frequent signet ring cell differentiation, rectal and sigmoid involvement, and adverse morphologic features

Abstract

Recent literature suggests an increasing incidence of colorectal carcinoma in young patients. We performed a histologic, molecular, and immunophenotypic analysis of patients with sporadic early-onset (r40 years of age) colorectal carcinoma seen at our institution from the years 2000-2010 and compared these tumors to a cohort of consecutively resected colorectal carcinomas seen in patients 440 years of age. A total of 1160 primary colorectal adenocarcinomas were surgically resected for the years 2000 through 2010. Of these, 75 (6%) were diagnoses in patients r40 years of age of which 13 (17%) demonstrated abnormalities in DNA mismatch repair, 4 (5%) were in patients with known germline genetic disorders (two patients with familial adenomatous polyposis, one patient with juvenile polyposis, and one patient with Li-Fraumeni syndrome), and three patients (4%) had long-standing chronic inflammatory bowel disease. The sporadic early-onset colorectal carcinoma group comprised a total of 55 patients (55/1160, 5%) and were compared with a control group comprising 73 consecutively resected colorectal carcinomas with proficient DNA mismatch repair in patients 440 years of age. For the early-onset colorectal carcinoma group, most cases (33/55, 60%) were diagnosed between the age of 35 and 40 years of age. Compared with the control group, the early-onset colorectal carcinoma group was significantly different with respect to tumor location (Po0.007) with 80% (44/55 cases) identified in either the sigmoid colon (24/55, 44%) or rectum (20/55, 36%). Morphologically, early-onset colorectal carcinomas more frequently displayed adverse histologic features compared with the control colorectal carcinoma group such as signet ring cell differentiation (7/55, 13% vs 1/73, 1%, P ¼ 0.021), perineural invasion (16/55, 29% vs 8/73, 11%, P ¼ 0.009) and venous invasion (12/55, 22% vs 4/73, 6%, P ¼ 0.006). A precursor adenomatous lesion was less frequently identified in the early-onset colorectal carcinoma group compared with the control group (19/55, 35% vs 39/73, 53%, P ¼ 0.034). Of the early-onset colorectal carcinomas, only 2/45 cases (4%) demonstrated KRAS mutations compared with 11/73 (15%) of the control group colorectal adenocarcinomas harboring KRAS mutations, although this difference did not reach statistical significance (P ¼ 0.13). BRAF V600E mutations were not identified in the early-onset colorectal carcinoma group. No difference was identified between the two

Outcomes of Surgical Treatment of Primary Signet Ring Cell Carcinoma of the Colon and Rectum: 22 Cases Reviewed With Literature

“…10,13,14 Parallel with the previous studies, in the current study age and sex were shown not to have any significant effect on survival. 12,15,16 As opposed to a study suggesting that female sex had a worse effect on survival, it was found in the current study that there were no differences in survival between sexes. Although there are various data concerning the size of tumors in the literature, it was suggested that well-and moderately-differentiated carcinomas might be diagnosed at larger sizes (5.5-6.2 cm).…”

“…In line with the former publications, we diagnosed most signet ring cell cancers at advanced stages. 7,[11][12][13][14][15][16][17] Data published concerning lymphatic and vascular invasions are generally heterogeneous. In accordance with Tung et al 13 and Makino et al, 17 in our series metastasis tended to develop in lymph nodes and on peritoneal surfaces rather than in the liver.…”

“…Survival rates over a 5-year period in previous studies ranged between 9% and 36%. [10][11][12][13][14][15][16][17]21 Average survival time was reported to be between 20 and 45 months. 4,17,21 Similar to the results in our study, the mean overall survival and mean progression-free survival times were found to be 33.3 6 7.1 months (95% CI, 19.4-57.2 months) and 11.8 6 3.5 months (95% CI, 4.9-18.7 months), respectively.…”

High Prevalence of Hereditary Cancer Syndromes in Adolescents and Young Adults With Colorectal Cancer

“…15 Of the patients with a hereditary cancer syndrome, one third were diagnosed with LS and one third had mutationnegative LS. Six patients with mutation-negative LS had incomplete work-ups for several reasons; therefore, we suspect that the number of patients with CRC who had mutation-positive LS could be higher than what is reported here.…”

Hereditary Colorectal Cancer Registries in Canada: Report from the Colorectal Cancer Association of Canada Consensus Meeting; Montreal, Quebec; October 28, 2011

“…The foregoing conditions represent the most common of the known hereditary crc (hcrc) syndromes, with lifetime risks for crc as high as 80% for ls and approaching 100% for map and fap when left untreated 8 . Three additional groups at high risk for crc or polyposis include families with familial colorectal cancer type X 9 , families with unexplained polyposis 10 , and people diagnosed with crc at very young ages (≤40 years) 11 . Although the genetic causes in each of these groups is unclear, hcrcrs play a large role in the identification and characterization of high-risk families, in gene discovery efforts, and in determining the best available clinical management 9,10,12,13 .…”