title: Flow cytometric DNA ploidy and S-phase fraction correlate with histopathologic indicators of tumor behavior in colorectal carcinoma.
abstract: BACKGROUND
  The clinical behavior of colorectal carcinoma is highly variable without reliable predictive biomarkers. Previous reports have shown that flow cytometric DNA analysis may provide valuable prognostic information in these tumors.
  
  
  OBJECTIVE
  This study evaluates the DNA ploidy and the S-phase fraction (SPF) on frozen samples obtained from 61 patients with colorectal carcinoma by using flow cytometry, and it correlates the data with histopathologic features known to affect disease prognosis. Tumors were classified using the World Health Organization's histologic criteria and were staged according the American Joint Committee on Cancer's classification system. Grade of the neoplasm, vascular invasion, and perineural tumor spread were evaluated in every case.
  
  
  RESULTS
  Fifty-nine percent of tumors were aneuploid and showed statistically significant higher S-phase values than diploid tumors (22.5 vs. 11.2 percent; P < 0.00001). Mean SPF of the whole series was 17.9 (range, 4.2-44.2) percent. A statistically significant association was found between SPF values and histologic grade (P < 0.0016), nodal status (P < 0.0007), distant metastasis (P < 0.0001), tumor stage (P < 0.0001), venous invasion (P < 0.0002), and lymphatic permeation (P < 0.01) but not with perineural growth and infiltration of the neoplasm through the bowel wall (T). DNA ploidy correlated positively with tumor stage (P < 0.03), and the association between aneuploidy and advanced stages of the disease was statistically significant.
  
  
  CONCLUSIONS
  These findings showed that flow cytometric DNA ploidy and SPF, evaluated in fresh samples, are potentially useful parameters to estimate colorectal carcinoma biopathology. Aneuploidy and high replicative neoplastic activity correlated with histopathologic features that are commonly associated with the prognosis of colorectal carcinoma, being SPF-related to disease dissemination and, therefore, an indicator of clinical relevance.
authors.affiliation: Departamento de Patologia Morfológica, Instituto Português de Oncologia de Francisco Gentil, Lisboa, Portugal.
authors.forename: A E
authors.initials: AE
authors.lastname: Pinto
authors.forename: P
authors.initials: P
authors.lastname: Chaves
authors.forename: P
authors.initials: P
authors.lastname: Fidalgo
authors.forename: A G
authors.initials: AG
authors.lastname: Oliveira
authors.forename: C N
authors.initials: CN
authors.lastname: Leitão
authors.forename: J
authors.initials: J
authors.lastname: Soares
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000782:Aneuploidy; D014408:Biomarkers, Tumor; D015179:Colorectal Neoplasms / Q000473:pathology*; D004273:DNA, Neoplasm / Q000032:analysis*; D005260:Female; D005434:Flow Cytometry / Q000379:methods / Q000592:standards*; D006652:Histological Techniques / Q000592:standards; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011003:Ploidies; D011379:Prognosis; D015203:Reproducibility of Results; D016196:S Phase
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm