COPPS, a composite score integrating pathological features, PS100 and SDHB losses, predicts the risk of metastasis and progression-free survival in pheochromocytomas/paragangliomas
VIRCHOWS ARCHIV
Authors: Pierre, Charlie; Agopiantz, Mikael; Brunaud, Laurent; Battaglia-Hsu, Shyue-Fang; Max, Antoine; Pouget, Celso; Nomine, Claire; Lomazzi, Sandra; Vignaud, Jean-Michel; Weryha, Georges; Oussalah, Abderrahim; Gauchotte, Guillaume; Busby-Venner, Helene
Abstract
Current histoprognostic parameters and prognostic scores used in paragangliomas and pheochromocytomas do not adequately predict the risk of metastastic progression and survival. Here, using a series of 147 cases of paraganglioma and pheochromocytoma, we designed and evaluated the potential of a new score, the COPPS (COmposite Pheochromocytoma/paraganglioma Prognostic Score), by taking into consideration three clinico-pathological features (including tumor size, necrosis, and vascular invasion), and the losses of PS100 and SDHB immunostain to predict the risk of metastasis. We compared also the performance of the COPPS with several presently used histoprognostic parameters in risk assessment of these tumors. A PASS score (Pheochromocytoma of the Adrenal gland Scaled Score) >= 6 was significantly associated with the occurrence of metastases (P < 0.0001) and shorter PFS (P = 0.013). In addition, both MCM6 and Ki-67 LI correlated with worse PFS (P = 0.004 and P < 0.0001, respectively), and MCM6, but not Ki-67, was significantly higher in metastatic group (P = 0.0004). Loss of PS100 staining correlated with the occurrence of metastasis (P < 0.0001) and shorter PFS (P < 0.0001). At a value of greater or equal to 3, the COPPS correlated with shorter PFS (P < 0.0001), and predicted reproducibly (weighted Kappa coefficient, 0.863) the occurrence of metastases with a sensitivity of 100.0% and specificity of 94.7%. It thus surpassed those found for either PASS, SDHB, MCM6, or Ki-67 alone. In conclusion, while validation is still necessary in independent confirmatory cohorts, COPPS could be of great potential for the risk assessment of metastasis and progression in paragangliomas and pheochromocytomas.
An interaction network driven approach for identifying biomarkers for progressing cervical intraepithelial neoplasia
SCIENTIFIC REPORTS
Authors: Suman, Shikha; Mishra, Ashutosh
Abstract
Overlapping genes across high-grade squamous intraepithelial lesions (CIN2 and 3) and cancer may serve as potential biomarkers for this progressive disease. Differentially expressed genes (DEGs) of dysplastic (CIN2 and CIN3) and cancer cells were identified by microarray data analysis. Gene interaction network was constructed using the 98 common DEGs among the dysplastic and cancer cells and analysed for the identification of common modules, hubs and significant motifs. Two significant modules and 10 hubs of the common gene interaction network, with 125 nodes and 201 edges were found. DEGs namely NDC80, ZWINT, CDC7, MCM4, MCM2 and MCM6 were found to be common in both the significant modules as well as the hubs. Of these, ZWINT, CDC7, MCM4, MCM2 and MCM6 were further identified to be part of most significant motifs. This overlapping relationship provides a list of common disease related genes among pre-cancerous and cancer stages which could help in targeting the proliferating cancerous cells during onset. Capitalizing upon and targeting Minichromosome maintenance protein complex - specifically the MCM2, MCM4 and MCM6 subunits, ZWINT and CDC7 for experimental validation, may provide valuable insights in understanding and detection of progressing cervical neoplasia to cervical cancer at an early stage.