Could short tandem repeats (STR) analysis resolve specimen source contamination and ıdentity problems, and comparing STR analysis of non-neoplastic and neoplastic tissues of the same patient? - A preliminary study

Not uncommonly, a surgical pathologist faces challenges regarding interpretation of tissue fragments that morphologically do not fit to the specimen at hand, known as 'floaters'. This occurs as a result of carrying over tissue pieces from one case to another during specimen grossing and routine technical proccess in a pathology laboratory. Also tissue mix-up may pose significant medical and legal difficulties when mixed tissue contains a significant lesion or tumor. Short tandem repeat (STR) analysis has emerged as the method of choice for testing to resolve tissue contamination and mix-up that arise in a pathology laboratory. STRs are repetitive DNA sequences of 2–7 nucleotides, which are highly polymorphic regions of the human genome. By analysing multiple STR loci together, it has high discriminative power to distinguish two DNA sample. However, a growing number of studies have found the somatic instability of tumour tissue and the tissue DNA damages caused by formaldehide. Therefore, alterations of STR loci used in forensic practice are also possible. Also archival pathology specimens sometimes are a source in forensic identification or paternity testing, if no other material is available. In order to evaluate the genetic alterations caused by somatic instability of tumour tissue and the DNA damages caused by formalyn on STR loci, we studied specimens of 10 patients who have been operated for neoplasia. We compared STR analyses of formalyn-fixed normal tissues of 10 patients to each other. Also for each patient, we compared the STR analyses of formalyn-fixed normal tissue to a formalyn-fixed tumour tissue of the same patient. We found that all 10 cases can be differentiated from each other based on their results of STR analyses. We detected three kinds of STR changes between normal and tumor tissue: partial loss of one allele, occurrence of an additional allele and occurrence of a new allele instead of that found in normal tissue. The tumor lesion of 4 cases displayed partial loss of one allele, but in none of them one allele was completely lost. New alleles could be demonstrated in tumor lesions of 9 patients and in 2 of them the new alleles in the tumor tissue replaced the one found in normal tissue. These STR changes caused by genetic instability of tumor tissue and formaldehyde may ocasionally complicate the interpretation of STR analysing results. However, our results demonstrate that by the careful examination of the allelic pattern, the STR-based tissue identity testing can be applied to formalyn-fixed normal and tumor tissues to detect diagnostic errors relating to contamination or misidentification in pathology laboratories. This finding could give rise to important implications for patient safety in current laboratory protocols. Anahtar kelimeler: Doku karışıklığı, doku kimlik tespiti, STR analizi, kalite kontrol.