Clonal evaluation of prostate cancer molecular heterogeneity in biopsy samples by dual immunohistochemistry and dual RNA in situ hybridization.
Pavithra Dedigama-ArachchigeShannon CarskadonJia LiIan LovelessMohamed AlhamarJames O PeabodyHans StrickerDhananjay A ChitaleCraig G RogersMani MenonNilesh S GuptaTarek A BismarSean R WilliamsonNallasivam PalanisamyPublished in: Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc (2020)
Prostate cancer is frequently multifocal. Although there may be morphological variation, the genetic underpinnings of each tumor are not clearly understood. To assess the inter and intra tumor molecular heterogeneity in prostate biopsy samples, we developed a combined immunohistochemistry and RNA in situ hybridization method for the simultaneous evaluation of ERG, SPINK1, ETV1, and ETV4. Screening of 601 biopsy cores from 120 consecutive patients revealed multiple alterations in a mutually exclusive manner in 37% of patients, suggesting multifocal tumors with considerable genetic differences. Furthermore, the incidence of molecular heterogeneity was higher in African Americans patients compared with Caucasian American patients. About 47% of the biopsy cores with discontinuous tumor foci showed clonal differences with distinct molecular aberrations. ERG positivity occurred in low-grade cancer, whereas ETV4 expression was observed mostly in high-grade cancer. Further studies revealed correlation between the incidence of molecular markers and clinical and pathologic findings, suggesting potential implications for diagnostic pathology practice, such as defining dominant tumor nodules and discriminating juxtaposed but molecularly different tumors of different grade patterns.
Keyphrases
- prostate cancer
- end stage renal disease
- high grade
- newly diagnosed
- ejection fraction
- low grade
- acute lymphoblastic leukemia
- healthcare
- single cell
- squamous cell carcinoma
- primary care
- gene expression
- dna methylation
- copy number
- radiation therapy
- lymph node
- papillary thyroid
- patient reported
- fine needle aspiration
- quality improvement
- risk assessment
- lymph node metastasis
- benign prostatic hyperplasia