The Prevalence of PIK3CA Biomarker in Tumor Microenvironment of Human non-small Cell Lung Cancer

Abstract

Abstract Background. Phosphatidyl 3-kinases (PI3K) are a family of lipid kinases involved in many cellular processes, including cell growth, proliferation, differentiation, motility, and survival, that can inhibit therapy profoundly. NSCLC accounts for approximately 80% of all lung cancers and is further subtyped into adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. Somatic oncogenic alterations can further molecularly subdivide these NSCLC subtypes. The general objective of the current work was to study the prevalence of PIK3CA expression and mutations in tumor microenvironment of human NSCLC. Materials and Methods. Thirty-three paraffin blocks were utilized from NSCLC archival cases for further investigations by using immunohistochemical staining and PCR/sequencing techniques for examination of PI3KCA cellular expression and detection of mutation in exons 9 and / or 20 of PI3KCA, respectively. Results. Immunohistochemical results showed that PIK3CA protein was localized in the cytoplasm of NSCLC as brown granules. The rating of scores of PIK3CA immunostaining of archived NSCLC revealed that twenty six cases (78.8%) showed positive immunohistochemical staining while seven cases (21.2%) showed negative immune staining. PCR/sequencing results of exon 9 revealed six substitution mutations and three indels (insertion / deletion) mutations were observed in the alignment. It was found that all the observed SNP positions were novel except 74681. The novelty of each observed SNP was detected using the NCBI SNP detector and it was found that all the observed SNP positions were novel except 7468. PCR/sequencing results of exon 20 revealed that the alignment results of all the patient samples for exon 20 revealed the presence of SNPs in variants no. 3, 5, and 7. All of these variations were only substitution mutations of this PCR amplicons. The exact position of each observed mutation was mentioned in the NCBI reference sequences. Conclusion. The data in hands shows that PIK3CA-mutated NSCLC is a clinically and genetically heterogeneous group. This holds true for the AD and SQCC subgroups and strongly suggests that PIKCA mutations do not define a distinct lung cancer subgroup amendable to specific therapy. Rather, these mutations seem to represent passenger mutations widely distributed among the other genetically defined subgroups. The status PIK3CA mutation may serve as a prognostic factor of poor survival.