ABSTRACT
BACKGROUND: Hereditary non-polyposis colorectal cancer (HNPCC) (Lynch cancer family syndrome I (LCFS1) and II (LCFS2)) is one of the most common hereditary cancer disorders. HNPCC results from dominantly inherited germline mutations in mismatch repair (MMR) genes, leading to genomic instability and cancer. No predictive physical signs of HNPCC are available to date. AIMS: Increased complexity in tumour associated vascular growth has been reported. Here, we tested the hypothesis that an increased vascular network complexity is a phenotypic marker for LCFS2. METHODS: Fourteen subjects from an LCFS2 kindred (gene carriers, n=5; non-carriers, n=9) and 30 controls were examined. Fractal dimension (D) at two scales (D (1-46), and D (1-15), tortuosity (minimum path dimension, Dmin), and relative Lempel-Ziev complexity (L-Z) of the vascular networks from the lower gingival and vestibular oral mucosa were measured. RESULTS: LCFS2 networks exhibited a significantly increased overall complexity at both larger (D (1-46): 1.82 (0.04) v 1.68 (0.08); p<0.0001) and smaller (D (1-15): 1.51 (0.11) v 1.20 (0.09); p<0.0001) scales, increased destructured randomness (L-Z: 0.77 (0.09) v 0.56 (0.03); p<0.0001), and decreased vessel tortuosity (DMIN: 1.02 (0.03) v 1.07 (0.04); p=0.0005) compared with control patterns. The vascular networks of LCFS2 gene carriers showed higher complexity at the smaller scale (D (1-15): 1.59 (0.12) v 1.47 (0.07); p=0.034), and higher destructured randomness (L-Z: 0.85 (0.11) v 0.73 (0.05); p=0.013) than those of non-carriers. CONCLUSIONS: Increased oral vascular network complexity is a previously unrecognised phenotypic marker for LCFS2, and is related to gene mutation carrier status.
Subject(s)
Colorectal Neoplasms, Hereditary Nonpolyposis/blood supply , Mouth Mucosa/blood supply , Neovascularization, Pathologic , Adult , Aged , Base Pair Mismatch/genetics , Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , Colorectal Neoplasms, Hereditary Nonpolyposis/pathology , Female , Gingiva/blood supply , Heterozygote , Humans , Male , Middle Aged , Mutation/genetics , Neovascularization, Pathologic/genetics , Neovascularization, Pathologic/pathology , PhenotypeABSTRACT
The identification of hereditary non-polyposis colorectal cancer (HNPCC) is important not only for the patient, but also for family members who are at increased risk of developing cancer. To determine if measuring various pathobiologic features of the colon carcinomas is useful in separating sporadic from HNPCC tumors, the authors studied tumor tissues from 46 patients with HNPCC and compared them to 70 with sporadic colorectal carcinoma. Parameters investigated included DNA ploidy (flow cytometry), AgNOR count (by silver staining), microvessel density (immunohistochemistry), p53 and K-ras expression, and grade-related parameters. Diploid tumors were more frequent in patients with HNPCC (65% vs 40%, P < .02), thus confirming previous observations concerning such an association. Higher AgNOR counts and greater AgNOR areas were observed in sporadic tumors than in HNPCC (5.2 +/- 1.5 vs 4.5 +/- 1.8, P < .01). Hereditary tumors tended to be less vascularized, whereas oncogene expression and grade-related parameters did not show appreciable differences between the two types of tumors. In conclusion, some of the investigated parameters may contribute to defining the biologic profile of HNPCC. In addition, these findings support the clinical impression of a more favorable outcome that is frequently seen in HNPCC patients.
