Expression Analysis of P16, C-Myc, and MSin3A in Non- Small Cell Lung Cancer by Computer Aided Scoring andAnalysis (CASA)

Immunohistochemical analysis (IHC) of tissue microarray (TMA) slides enables large sets oftissue samples to be analyzed simultaneously on a single slide. However, manual evaluationof small cores on a TMA slide is time consuming and error prone. We describe a computeraided scoring and analysis (CASA) method to allow facile and reliable scoring of IHCstaining using TMA containing 300 non-small cell lung cancer (NSCLC) cases. In the twoprevious published papers utilizing our TMA slides of lung cancer we examined 18 proteinsinvolved in the chromatin machinery. We developed our study using more proteins of thechromatin complex and several transcription factors that facilitate the chromatin machinery.Then, a total of 78 antibodies were evaluated by CASA to derive a normalized intensity valuethat correlated with the overall staining status of the targeting protein. The intensity values forTMA cores were then examined for association to clinical variables and predictivesignificance individually and with other factors. Using our TMA, the intensity of severalprotein pairs were significantly correlated with an increased risk of death in NSCLC. Theseincluded c-Myc with p16, mSin3A with p16 and c-Myc with mSinA. Predictive values of thesepairs remained significant when evaluated based on standard IHC scores. Our resultsdemonstrate the usefulness of CASA a s a valuable tool for systematic assessment of TMAslides to identify potential predictive biomarkers using a large set of primary human tissues.

کلیدواژه ها:

Tissue Microarray ، Immunohistochemistry ، CASA ، NSCLC ، Expression