Homologous recombination deficiency (HRD) score in aggressive prostatic adenocarcinoma with or without intraductal carcinoma of the prostate (IDC-P)

Zhu, Sha; Zhao, Jinge; Nie, Ling; Yin, Wenlian; Zhang, Yaowen; Zhao, Fengnian; Ni, Yang; Zhang, Xingming; Wang, Zhipeng; Dai, Jindong; Liu, Zhenhua; Chen, Junru; Zeng, Yue; Wang, Zilin; Sun, Guangxi; Liang, Jiayu; Zhao, Xiaochen; Zhu, Xudong; Tao, Ronggui; Yang, Jiyu; He, Ben; Chen, Ni; Shen, Pengfei; Zeng, Hao

doi:10.1186/s12916-022-02430-0

Cited by 26 publications

(21 citation statements)

References 44 publications

(45 reference statements)

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“…Moreover, HRD with BRCA2 deletions may lead to a pathogenic MYC variant, which is closely associated with the progression of localized or castration‐naïve PC to CRPC. 31 Delayed diagnosis and treatment of patients with PC‐carrying BRCA2 deletions can lead to the epithelial–mesenchymal transition, followed by rapid disease progression due to DNA damage and genomic instability. 26 These findings strongly suggest that even heterozygous BRCA2 deletions can cause HRD due to loss of function and may accelerate the progression of localized PC to BCR and eventually CRPC.…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies suggest that tumors with BRCA2 deletions display pathological characteristics similar to those of intraductal carcinoma 29 and neuroendocrine differentiated tumors, 30 which are both poor prognostic indicators. Moreover, HRD with BRCA2 deletions may lead to a pathogenic MYC variant, which is closely associated with the progression of localized or castration‐naïve PC to CRPC 31 . Delayed diagnosis and treatment of patients with PC‐carrying BRCA2 deletions can lead to the epithelial–mesenchymal transition, followed by rapid disease progression due to DNA damage and genomic instability 26 .…”

Section: Discussionmentioning

confidence: 99%

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Estimating copy number to determine BRCA2 deletion status and to expect prognosis in localized prostate cancer

et al. 2023

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Background The significance of BRCA alterations has been implicated in the development of metastatic castration‐resistant prostate cancer (PC). The details of the frequency and significance of BRCA alterations in localized PC remain unknown. In this study, we investigated the frequency and clinical significance of BRCA alterations in localized PCs using an in‐house next‐generation sequencer (NGS) system. Methods DNA was extracted from formalin‐fixed paraffin‐embedded tissues of surgical specimens from 126 patients with clinically localized PC who underwent radical prostatectomy. The mutation information of 164 cancer genes was analyzed using the PleSSision‐Rapid test. Both copy number (CN) variation and loss of heterozygosity of various genes, such as BRCA1 and BRCA2, were estimated and reported. Results Next‐generation sequencer analyses revealed that the BRCA2 CN was decreased in 17 patients (13.5%) and the BRCA1 CN in six (4.8%) patients. NGS‐based CN values were shown to be highly correlated with droplet digital PCR‐based CN values. Tissue‐specific BRCA expression investigated using the Human Protein Atlas showed that the decreased CN of BRCA2, but not BRCA1, is responsible for the decreased BRCA activity in PC. Ten of the 22 patients with decreased BRCA2 CN were presumed to have somatic heterozygous deletion. There were no observed associations between the heterozygous deletion of BRCA2 and various clinicopathological parameters. Furthermore, three of 10 patients developed biochemical recurrence within 3 months after surgery. Multivariate analyses revealed that the initial prostate‐specific antigen levels and BRCA2 CN were independent factors for biochemical recurrence. Conclusion Our results suggest that a decrease in BRCA2 CN may be used as a biomarker for predicting recurrence after surgery in localized PC. Early screening for somatic alterations in BRCA2 using NGS may help to broadly predict the risk of PC progression.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Estimating copy number to determine BRCA2 deletion status and to expect prognosis in localized prostate cancer

et al. 2023

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“…Thus, IDC-P patients are more likely to carry the BRCA2 gene or BRCA-like molecular alterations. These molecular characteristic changes suggest that PARP inhibitors, represented by olaparib, are among the therapeutic options for improving the clinical prognosis of IDC-P positive patients ( 29 ).…”

Section: Discussionmentioning

confidence: 99%

Construction and validation of a clinical predictive nomogram for intraductal carcinoma of the prostate based on Chinese multicenter clinical data

Yang

Zhang²,

Li³

et al. 2022

Front. Oncol.

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IntroductionIntraductal carcinoma of the prostate (IDC-P) is a special pathological type of prostate cancer that is highly aggressive with poor prognostic outcomes.ObjectiveTo establish an effective predictive model for predicting IDC-P.MethodsData for 3185 patients diagnosed with prostate cancer at three medical centers in China from October 2012 to April 2022 were retrospectively analyzed. One cohort (G cohort) consisting of 2384 patients from Zhejiang Provincial People’s Hospital was selected for construction (Ga cohort) and internal validate (Gb cohort)of the model. Another cohort (I cohort) with 344 patients from Quzhou People’s Hospital and 430 patients from Jiaxing Second People’s Hospital was used for external validation. Univariate and multivariate binary logistic regression analyses were performed to identify the independent predictors. Then, the selected predictors were then used to establish the predictive nomogram. The apparent performance of the model was evaluated via externally validated. Decision curve analysis was also performed to assess the clinical utility of the developed model.ResultsUnivariate and multivariate logistic regression analyses showed that alkaline phosphatase (ALP), total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), prostate specific antigen (PSA) and lactate dehydrogenase were independent predictors of IDC-P. Therefore, a predictive nomogram of IDC-P was constructed. The nomogram had a good discriminatory power (AUC = 0.794). Internal validation (AUC = 0.819)and external validation (AUC = 0.903) also revealed a good predictive ability. Calibration curves showed good agreement between the predicted and observed incidences of IDC-P.ConclusionWe developed a clinical predictive model composed of alkaline phosphatase (ALP), total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), prostate specific antigen (PSA) and lactate dehydrogenase (LDH) with a high precision and universality. This model provides a novel calculator for predicting the diagnosis of IDC-P and different treatment options for patients at an early stage.

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“…A recent study of patient-derived tumor xenografts (PDX) in three carriers of germline BRCA2 mutations found that PDX of BRCA2-mutant tumors had a significantly higher incidence of IDC-P compared to PDX established from sporadic prostate cancer (42% vs. 9%, p = 0.015). 78 Zhu et al 79 performed homologous recombination deficiency (HRD) score analysis in 123 prostate cancer patients with untreated high-risk M0 and de novo M1 disease, with and without IDC-P. The HRD score, which directly results from the loss of homologous recombinant repair (HRR) function (genomic scars), is a result-oriented method of expressing genomic instability.…”

Section: Dna Damage Repair Gene Mutationsmentioning

confidence: 99%

Recent insights on the clinical, pathological, and molecular features of intraductal carcinoma of the prostate

Naito,

Kato,

Nagayama

et al. 2023

Int J of Urology

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Intraductal carcinoma of the prostate, a unique histopathologic entity that is often observed (especially in advanced prostate cancer), is characterized by the proliferation of malignant cells within normal acini or ducts surrounded by a basement membrane. Intraductal carcinoma of the prostate is almost invariably associated with an adjacent high‐grade carcinoma and is occasionally observed as an isolated subtype. Intraductal carcinoma of the prostate has been demonstrated to be an independent poor prognostic factor for all stages of cancer, whether localized, de novo metastatic, or castration‐resistant. It also has a characteristic genetic profile, including high genomic instability. Recognizing and differentiating it from other pathologies is therefore important in patient management, and morphological diagnostic criteria for intraductal carcinoma of the prostate have been established. This review summarizes and outlines the clinical and pathological features, differential diagnosis, molecular aspects, and management of intraductal carcinoma of the prostate, as described in previous studies. We also present a discussion and future perspectives regarding intraductal carcinoma of the prostate.

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Homologous recombination deficiency (HRD) score in aggressive prostatic adenocarcinoma with or without intraductal carcinoma of the prostate (IDC-P)

Cited by 26 publications

References 44 publications

Estimating copy number to determine BRCA2 deletion status and to expect prognosis in localized prostate cancer

Estimating copy number to determine BRCA2 deletion status and to expect prognosis in localized prostate cancer

Construction and validation of a clinical predictive nomogram for intraductal carcinoma of the prostate based on Chinese multicenter clinical data

Recent insights on the clinical, pathological, and molecular features of intraductal carcinoma of the prostate

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