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Urothelial Carcinoma of the Bladder: Identification of Genetic Signatures and Correlation With Clinical Outcomes [Meeting Abstract]

Ren, Qinghu; Kim, Philip; Cha, Eugene; Sfakianos, John; Iyer, Gopa; Scott, Sasinya; Gandhi, Anupama; Shah, Ronok; Bajorin, Dean; Rosenberg, Jonathan; Schultz, Nikolaus; Berger, Michael; Solit, David; Chen, Ying-Bei; Sirintrapun, Sahussapont; Gopalan, Anuradha; Fine, Samson; Tickoo, Satish; Reuter, Victor; Bochner, Bernard; Al-Ahmadie, Hikmat
ISSN: 1530-0307
CID: 2245822


Bagrodia, Aditya; Cha, Eugene; Sfakianos, John; Iyer, Gopa; Lee, Byron; Scott, Sasinya; Zabor, Emily; Shah, Ronak; Ren, Qinghu; Kim, Philip; Hakimi, Ari; Ostrovnaya, Irina; Rosenberg, Jonathan; Dalbagni, Guido; Bajorin, Dean; Reuter, Victor; Berger, Michael; Bochner, Bernard; Al-Ahmadie, Hikmat; Solit, David; Coleman, Jonathan
ISSN: 1527-3792
CID: 2245832

Re-evaluating the concept of "dominant/index tumor nodule" in multifocal prostate cancer

Huang, Cheng Cheng; Deng, Fang-Ming; Kong, Max X; Ren, Qinhu; Melamed, Jonathan; Zhou, Ming
Prostate cancer (PCa) often presents as a multifocal disease with heterogeneity in Gleason score (GS) and genetic alterations. Dominant/index tumor nodule (DN), the largest nodule in a multifocal disease, is presumed to harbor the most aggressive biological behavior and therefore dictate the overall clinical behavior of PCa. In this study, we examined the pathological features of DN and re-evaluated the validity of the "DN" concept in multifocal PCa. A total of 201 consecutive radical prostatectomy specimens were totally submitted and examined. All independent cancer foci were recorded with prognostically important pathological parameters. Unifocal and multifocal disease was present in 25 (12.4 %) and 176 (87.6 %) cases, respectively. In 20 (11.3 %) multifocal cases, the highest GS, the largest tumor volume (TV), and extraprostatic extension (EPE) did not concur in the same tumor nodules. Non-DNs had a higher GS and EPE in 13 cases each and had both the highest GS and EPE in 5 cases. In the majority of multifocal prostate cancer (88.7 %), DNs have the highest GS and EPE. In these cases, DN is still a valid concept and can be used for assigning overall GS and procuring tissue for research. However, in a significant number of cases (11.3 %), the largest TV, the highest GS, and EPE did not concur in the same tumor nodules. In these cases, pathologists should de-emphasize the concept of DN. Instead, they should place the emphasis on the multifocal nature of the disease and document the pathological features of all independent tumor foci that have the largest TV, the highest GS, and EPE.
PMID: 24619626
ISSN: 0945-6317
CID: 970002

Epithelial and stromal expression of miRNAs during prostate cancer progression

Ren, Qinghu; Liang, Jiaqian; Wei, Jianjun; Basturk, Olca; Wang, Jinhua; Daniels, Garrett; Gellert, Lan Lin; Li, Yirong; Shen, Ying; Osman, Iman; Zhao, Jun; Melamed, Jonathan; Lee, Peng
Global microRNA (miRNA) profile may predict prostate cancer (PCa) behaviors. In this study, we examined global miRNA expression by miRNA profiling as well as specific miRNA expression levels in PCa epithelium and stroma by in situ hybridization (ISH) and correlated with various clinicopathological features. We first performed comprehensive miRNA profiling on 27 macrodissected cases of PCa by miRNA microarray. A total of 299 miRNAs were significantly dysregulated in high grade and advanced stage PCa. We demonstrated that PCa can be readily classified into high grade/stage and low-grade/stage groups by its global miRNA expression profile. Next, we examined the expression of several selected dysregulated miRNAs, including let-7c, miR-21, miR-27a, miR-30c, and miR-219, in PCa by ISH. The levels of miRNA expression in epithelial and stromal cells were scored semiquantitatively and compared with clinicopathological features, including age, race, Gleason score, stage, PSA recurrence, metastasis, hormone resistance and survival. We found that the expression of miR-30c and miR-219 were significantly down-regulated in PCa. miR-21 and miR-30c were significantly down-regulated in PCa in African Americans compared to Caucasian Americans. In addition, down-regulation of let-7c, miR-21, miR-30c, and miR-219 are associated with metastatic disease. Furthermore, down-regulation of miR-30c and let-7c are significantly associated with androgen-dependent PCa. In PCa stromal cells, let-7c downregulation is significantly associated with extraprostatic extension. Our data suggest that selected miRNAs may serve as potential biomarkers to predict cancer progression.
PMID: 25075250
ISSN: 1943-8141
CID: 1105942


Wu, Xinyu; Li, Yirong; Du, Xinxin; Ren, Qinghu; Kong, Max X; Wang, Jinhua; Wang, LingHang; Yang, Yang; Zhang, Valerio; Zhang, David; Ye, Fei; Daniels, Garrett; Deng, Fangming; Wei, Jianjun; Melamed, Jonathan; Monaco, Marie E; Lee, Peng
ISSN: 1527-3792
CID: 2245772


Sfakianos, John P; Kim, Philip H; Iyer, Gopa; Cha, Eugene K; Zabor, Emily C; Hakimi, AA; Scott, Sasinya N; Ramirez, Ricardo; Hanrahan, Aphrothiti J; Rosenberg, Jonathan E; Al-Ahmadie, Hikmat; Ren, Qinghu; Dalbagni, Guido; Bajorin, Dean F; Berger, Michael F; Bochner, Bernard H; Solit, David B; Coleman, Jonathan A
ISSN: 1527-3792
CID: 2245782


Sfakianos, John P; Cha, Eugene K; Kim, Philip H; Iyer, Gopa; Hakimi, AA; Scott, Sasinya N; Ramirez, Ricardo; Hanrahan, Aphrothiti J; Rosenberg, Jonathan E; Ren, Qinghu; Al-Ahmadie, Hikmat; Dalbagni, Guido; Bajorin, Dean F; Berger, Michael F; Bochner, Bernard H; Solit, David B; Coleman, Jonathan A
ISSN: 1527-3792
CID: 2245812

Expression of androgen receptor and its phosphorylated forms in breast cancer progression

Ren, Qinghu; Zhang, Liying; Ruoff, Rachel; Ha, Susan; Wang, Jinhua; Jain, Shilpa; Reuter, Victor; Gerald, William; Giri, Dilip D; Melamed, Jonathan; Garabedian, Michael J; Lee, Peng; Logan, Susan K
BACKGROUND: Androgen receptor (AR) expression in breast cancers may serve as a prognostic and predictive marker. We examined the expression pattern of AR and its phosphorylated forms, Ser-213 (AR-Ser[P]-213) and Ser-650 (AR-Ser[P]-650), in breast cancer and evaluated their association with clinicopathological parameters. METHODS: Immunohistochemistry was performed on primary and distant metastatic breast cancers and benign breast tissue using antibodies against AR, AR-Ser(P)-213, and AR-Ser(P)-650. The levels of cytoplasmic and nuclear expression were scored semiquantitatively using a histoscore. RESULTS: Nuclear staining of AR was observed in all benign breast tissue and 67% of cancer cases. Nuclear and cytoplasmic AR-Ser(P)-213 was increased in breast cancers 2-fold (P = .0014) and 1.7-fold (P = .05), respectively, compared with benign controls, whereas nuclear and cytoplasmic AR-Ser(P)-650 expression was decreased in tumors by 1.9-fold and 1.7-fold (both P < .0001), respectively. Increased expression of nuclear or cytoplasmic AR-Ser(P)-213 was observed in metastatic breast cancers (1.3-fold, P = .05), ER-negative (2.6-fold, P = .001), and invasive ductal carcinoma (6.8-fold, P = .04). AR-Ser(P)-650 expression was downregulated in lymph node-positive breast cancers (1.4-fold, P = .02) but was upregulated in invasive ductal carcinomas (3.2-fold, P < .0001) and metastases (1.5-fold, P = .003). Moreover, in ER-negative breast cancers, nuclear AR-Ser(P)-650 was decreased (1.4-fold, P = .005), and cytoplasmic AR-Ser(P)-650 was increased (1.4-fold, P = .003). CONCLUSIONS: AR and its phosphorylation at serines 213 and 650 are differentially expressed in breast cancer tumorigenesis and progression. Phosphorylation of AR at serines 213 and 650 is increased in ER-negative breast cancers, ductal carcinomas, and metastases and may have predictive value in breast cancer prognosis. Cancer 2013;000:000-000. (c) 2013 American Cancer Society.
PMID: 23605249
ISSN: 0008-543x
CID: 302392

Gleason 6 Prostate Tumors Diagnosed in the PSA Era Do Not Demonstrate the Capacity for Metastatic Spread at the Time of Radical Prostatectomy

Donin, Nicholas M; Laze, Juliana; Zhou, Ming; Ren, Qinghu; Lepor, Herbert
OBJECTIVE: To elucidate the probability that Gleason 6 tumors diagnosed in the prostate-specific antigen (PSA) era treated with radical prostatectomy (RP) develop metastasis. METHODS: Between October 2000 and June 2012, 1781 men underwent open RP by a single surgeon. Biochemical recurrence (BCR) was defined as a serum PSA value >/=0.2 ng/mL, or 2 progressively rising PSA values >0.14 ng/mL. Significant BCR (sBCR) was defined as a BCR with a PSA doubling time (PSADT) <36 months. Insignificant BCR (iBCR) was defined as BCR with a PSADT >/=36 months. RESULTS: Eight hundred fifty-seven of men (48.1%) undergoing open RP had a pathologic diagnosis of Gleason 6. Twenty-three of 857 of these men (2.7%) developed BCR, 7 were designated as iBCR (mean PSADT 81 months, range 36 to 100), 16 were sBCR (mean PSADT 8 months, range 1.5-20 months). There was a 10-fold difference in PSADT between the sBCR and iBCR groups (P <.001). All men with sBCR underwent salvage radiation therapy (SRT) and all demonstrated a subsequent PSA decline to
PMID: 23706588
ISSN: 0090-4295
CID: 415042

Prostate Cancer Multifocality and Heterogeneity: Implications for Gleason Grading, Tumor Volume Measurement and Tissue Sampling for Research [Meeting Abstract]

Huang, C. C.; Kong, M.; Ren, Q.; Deng, F-M; Melamed, J.; Zhou, M.
ISSN: 0893-3952
CID: 227142