title: Molecular profiling in fresh tissue with high tumor cell content promotes enrichment for aggressive adenocarcinomas in cervix.
abstract: Many emerging tools for comprehensive molecular profiling of malignant lesions demand fresh frozen tissue with a high tumor purity. Often, a tumor epithelial content of at least 80% is recommended. This approach may lead to a systematic bias, and therefore we explore if this introduces a selection of cases with a certain phenotype in cervical cancer. Clinicopathologic data for a population-based cohort of 328 patients have been studied. Fresh frozen tumor specimens were available for 151 of these patients and investigated for epithelial tumor cell portion in hematoxylin-stained frozen sections by light microscopy. The estimated tumor purity in the samples was compared with FIGO stage, histopathologic characteristics and survival. High tumor purity was significantly more often found in squamous cell carcinoma (SCC) compared to adenocarcinoma (AC) (P=0.03). For the subgroup of AC (n=40), there was a significant association between high tumor purity in the fresh frozen samples and later occurrence of recurrent disease (P=0.04). In SCC, no significant associations between tumor purity and disease stage, grade or outcome were found. Apparently in line with this, grade was found to influence prognosis in AC, but not in SCC. Our findings suggest that selection of samples based on high tumor purity in fresh frozen tissue may introduce a selection bias toward aggressive disease for the subgroup of AC, but not for SCC of the cervix. Thus, the prevalence of potential molecular biomarkers identified in AC in particular should be validated in a population-based setting to further explore clinical relevance. Also, molecular biomarkers only prevalent in subgroups with low tumor purity may go undetected in sample collections enriched for high tumor purity.
authors.affiliation: Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway; Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway. Electronic address: Mari.Halle@k2.uib.no.
authors.forename: Mari Kyllesø
authors.initials: MK
authors.lastname: Halle
authors.affiliation: Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway; Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: Camilla
authors.initials: C
authors.lastname: Krakstad
authors.affiliation: Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway; Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: Hilde
authors.initials: H
authors.lastname: Engerud
authors.affiliation: Department of Pathology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Bjørn
authors.initials: B
authors.lastname: Bertelsen
authors.affiliation: Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway; Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: Helga B
authors.initials: HB
authors.lastname: Salvesen
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D002584:Cervix Uteri / Q000378:metabolism / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D005629:Frozen Sections; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D016612:Paraffin Embedding; D010641:Phenotype; D011379:Prognosis; D013048:Specimen Handling; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor
keywords: Adenocarcinoma; Cervical cancer; Prognosis; Snap frozen fresh tissue; Tumor cell content