title: Histochemical and immunohistochemical evidence of tumor heterogeneity in colorectal cancer.
abstract: BACKGROUND
  Intratumoral heterogeneity implies the existence of differences between tumor cells, which can best be shown by histochemical and immunohistochemical techniques. The histological study is a mandatory step in any research aimed at characterizing tumor heterogeneity. Immunohistochemistry (IHC) also plays an important role in the differentiation of tumor types, assessing aggressiveness.
  
  
  METHODS
  Investigated group consisted of 50 patients with colorectal adenocarcinoma, for each were recorded clinicopathological data and harvested samples intraoperatively, which were included in paraffin blocks. We perform Hematoxylin-Eosin staining for histological grade and other indices. IHC study used Avidin-Biotin-Peroxidase (ABC), with the markers: CK7, CK20, MUC1, MUC2, Ki-67, PCNA, p53, KRAS, BCL2, PTEN, EGFR. The resulting data were analyzed by statistical methods.
  
  
  RESULTS
  Most of colorectal adenocarcinoma studied had no special histological features and had G2 grade. IHC detected in most cases the CK20+÷CK7- phenotype (78%) and MUC1 (74%) protein expression. The proliferation markers (Ki-67 and PCNA) were present in all tumor mass with a variable index, which shows high intratumoral heterogeneity, but p53 and KRAS were distributed more uniformly, showing low intratumoral heterogeneity. PTEN was expressed nuclearly in 86% of the cases and EGFR in 42%.
  
  
  CONCLUSIONS
  The expression profiles of cytokeratins and mucins in the colorectal adenocarcinomas are useful in defining tumor phenotypes with different prognosis and therapy. We found a significant positive correlation between KRAS protein expression and BCL2 and TP53 expression. The study demonstrated the intratumoral and intertumoral heterogeneity, expressed at phenotypic level.
authors.affiliation: Department of Microbiology, University of Medicine and Pharmacy of Craiova, Romania; ovidiu.zlatian@gmail.com.
authors.forename: Ovidiu Mircea
authors.initials: OM
authors.lastname: Zlatian
authors.forename: Maria Victoria
authors.initials: MV
authors.lastname: Comănescu
authors.forename: Alexandra Floriana
authors.initials: AF
authors.lastname: Roşu
authors.forename: Lucica
authors.initials: L
authors.lastname: Roşu
authors.forename: Mihai
authors.initials: M
authors.lastname: Cruce
authors.forename: Alice Elena
authors.initials: AE
authors.lastname: Găman
authors.forename: Cornelia Daniela
authors.initials: CD
authors.lastname: Călina
authors.forename: Veronica
authors.initials: V
authors.lastname: Sfredel
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D002288:Adenocarcinoma, Mucinous / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D053554:Keratin-20 / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009077:Mucins / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D010641:Phenotype; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C507499:KRT20 protein, human; D053554:Keratin-20; D019394:Ki-67 Antigen; D009077:Mucins; D018809:Proliferating Cell Nuclear Antigen; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human