Intraductal Carcinoma Of The Prostate Research Articles

Feasibility study of ADCs targeting TROP-2, HER2, and CD46 in Ductal Adenocarcinoma and Intraductal Carcinoma of the prostate.

Ductal Adenocarcinoma (DAC) and Intraductal Carcinoma of the Prostate (IDC-P) respond poorly to all the currently available conventional therapies. Given their accurate and efficient elimination of cancer cells, Antibody-Drug Conjugates (ADCs) have become one of the most promising anticancer treatments. However, no ADCs have so far been approved for Prostate Cancer (PCa) treatment. This study investigated TROP-2, HER2, and CD46 expression in DAC/IDC-P samples, indirectly analyzing their preliminary feasibility as therapeutic targets for future treatment of the two conditions. We conducted a retrospective study involving 184 participants (87 DAC/IDC-P patients and 97 Prostatic Acinar Adenocarcinoma (PAC) patients with a Gleason score ≥ 8) without prior treatment between August 2017 and August 2022. Immunohistochemical staining was employed to detect the differential protein expressions of TROP-2, HER2, and CD46 in DAC/IDC-P, PAC, and normal prostate tissues. Compared to pure PAC tissues, TROP-2 expression was significantly higher in DAC/IDC-P and DAC/IDC-P-adjacent PAC tissues (H-score 68.8 vs. 43.8, p < 0.001, and 59.8 vs. 43.8, p = 0.022, respectively). No significant differences in HER2 expression were observed across different cancer tissues. Compared to both DAC/IDC-P-adjacent PAC and pure PAC tissues, CD46 expression was significantly higher in DAC/IDC-P tissues (42.3 vs. 28.6, p = 0.041, and 42.3 vs. 24.3, p = 0.0035, respectively). Herein, TROP-2 and CD46 expression was higher in DAC/IDC-P tissues than in pure PAC and normal prostate tissues. This finding implies that ADCs targeting the two proteins hold significant promise as potential future treatments for DAC/IDC-P.

Unveiling the pathologic predictor in patients with metastatic hormone-sensitive prostate cancer treated with abiraterone: Intraductal carcinoma of the prostate and its subtypes.

Unveiling the pathologic predictor in patients with metastatic hormone-sensitive prostate cancer treated with abiraterone: Intraductal carcinoma of the prostate and its subtypes.

Unveiling the Genomic Landscape of Intraductal Carcinoma of the Prostate Using Spatial Gene Expression Analysis.

Intraductal carcinoma of the prostate (IDCP) has recently attracted increasing interest owing to its unfavorable prognoses. To effectively identify the IDCP-specific gene expression profile, we took a novel approach of characterizing a typical IDCP case using spatial gene expression analysis. A formalin-fixed, paraffin-embedded sample was subjected to Visium CytAssist Spatial Gene Expression analysis. IDCP within invasive prostate cancer sites was recognized as a distinct cluster separate from other invasive cancer clusters. Highly expressed genes defining the IDCP cluster, such as MUC6, MYO16, NPY, and KLK12, reflected the aggressive nature of high-grade prostate cancer. IDCP sites also showed increased hypoxia markers HIF1A, BNIP3L, PDK1, and POGLUT1; decreased fibroblast markers COL1A2, DCN, and LUM; and decreased immune cell markers CCR5 and FCGR3A. Overall, these findings indicate that the hypoxic tumor microenvironment and reduced recruitment of fibroblasts and immune cells, which reflect morphological features of IDCP, may influence the aggressiveness of high-grade prostate cancer.

Clinical Management of Intraductal Carcinoma of the Prostate.

Intraductal carcinoma of the prostate (IDC-P) has emerged as a distinct entity with significant clinical implications in prostate cancer (PCa) management. Despite historically being considered an extension of invasive PCa, IDC-P shows unique biological characteristics that challenge traditional diagnostic and therapeutic settings. This review explores the clinical management of IDC-P. While the diagnosis of IDC-P relies on specific morphological criteria, its detection remains challenging due to inter-observer variability. Emerging evidence underscores the association of IDC-P with aggressive disease and poor clinical outcomes across various PCa stages. However, standardized management guidelines for IDC-P are lacking. Recent studies suggest considering adjuvant and neoadjuvant therapies in specific patient cohorts to improve outcomes and tailor treatment strategies based on the IDC-P status. However, the current level of evidence regarding this is low. Moving forward, a deeper understanding of the pathogenesis of IDC-P and its interaction with conventional PCa subtypes is crucial for refining risk stratification and therapeutic interventions.

Intraductal Carcinoma of the Prostate versus Simulants: A Differential Diagnosis Growing in Clinical Impact.

Despite its first recognition even longer ago, in the past nearly 20 years, intraductal carcinoma of the prostate has become a standard histopathologic reporting parameter conveying a strong negative prognostic factor for prostatic adenocarcinoma. When seen at biopsy, intraductal carcinoma of the prostate is associated with risk for aggressive prostatectomy outcomes, including frequently high-grade, high-stage, high-volume disease, with increased risk for recurrence and progression. Multiple organizations, including the uropathology subspecialty societies to the World Health Organization, recognize and recommend reporting the presence of intraductal carcinoma, whether sampled in "pure" form or present with concomitant invasive adenocarcinoma. Moreover, emerging scholarship relates intraductal carcinoma to higher prevalence of homologous recombination repair deficiency mutations in prostatic adenocarcinoma, whether somatic or germline, which serve as indications for approved targeted therapies. Taken together, this is a diagnosis for the histopathologist not to miss. In view of these elevated stakes and the opportunity to further precision medicine, this review details neoplastic and non-neoplastic simulants in the differential diagnosis of intraductal carcinoma of the prostate.

The presence of intraductal carcinoma of prostate is a risk factor for poor pathologic response in men with high-risk prostate cancer receiving neoadjuvant therapy

ObjectiveTo explore the potential association between the presence of intraductal carcinoma of the prostate (IDC-P) on biopsy and pathologic response of primary tumor to neoadjuvant therapy in patients with high-risk prostate cancer. MethodsEighty-five patients with high-risk localized/locally advanced prostate cancer (CaP) who were given 6-month neoadjuvant therapies of androgen deprivation therapy plus docetaxel or abiraterone prior to radical prostatectomy in 2 prospective trials were included in this study. The presence of IDC-P in biopsy pathology was rereviewed by 2 experienced pathologists. Favorable pathologic response was defined as pathologic complete response or minimal residual disease <5 mm on whole-mount histopathology. Characteristics of clinical and biopsy pathology variables were included in univariate and multivariate logistic regression analyses to identify risk factors for the prediction of favorable pathologic response on final pathology. ResultsIDC-P was identified to be present on biopsy pathology of 35 patients (41.2%) while favorable pathologic responses were confirmed in 25 patients (29.4%). Initial prostate-specific antigen (PSA) (OR 3.592, 95% CI 1.176–10.971, P = 0.025) and the presence of IDC-P on biopsy pathology (OR 3.837, 95% CI 1.234–11.930, P = 0.020) were found to be significantly associated with favorable pathologic response in multivariate logistic regression analysis. ConclusionIDC-P on biopsy pathology was found to be an independent risk factor to predict a poor pathology response of primary CaP to neoadjuvant therapies.

Identification of recurrent BRAF non-V600 mutations in intraductal carcinoma of the prostate in Chinese populations

While BRAF alterations have been established as a driver in various solid malignancies, the characterization of BRAF alterations in prostate cancer (PCa) has not been thoroughly interrogated. By bioinformatics analysis, we first found that BRAF alterations were associated with advanced PCa and exhibited mutually exclusive pattern with ERG alteration across multiple cohorts. Of the most interest, recurrent non-V600 BRAF mutations were found in 3 of 21 (14.3 %) PCa patients demonstrating IDC-P morphology. Furthermore, experimental overexpression of BRAFK601E and BRAFL597R exhibited emergence of oncogenic phenotypes with intensified MAPK signaling in vitro, which could be targeted by MEK inhibitors. Comparison of the incidence of BRAF alterations in IDC-P between western and Chinese ancestry revealed an increased prevalence in the Chinese population. The BRAF mutation may represent important genetic alteration in a subset of IDC-P, highlighting the role of MAPK signaling pathway in this subtype of PCa. To the best of knowledge, this is the first description of non-V600 BRAF mutation in setting of IDC-P, which may in part explain the aggressive phenotype seen in IDC-P and could also bring more treatment options for PCa patients with IDC-P harboring such mutations.

Genomic mutations and homologous recombination deficiency (HRD) score in Japanese patients with metastatic hormone-sensitive prostate cancer (mHSPC): The impact of intraductal carcinoma of the prostate (IDC-P).

Genomic mutations and homologous recombination deficiency (HRD) score in Japanese patients with metastatic hormone-sensitive prostate cancer (mHSPC): The impact of intraductal carcinoma of the prostate (IDC-P).

Nomogram for predicting the overall survival and cancer-specific survival of patients with intraductal carcinoma of the prostate

PurposeIntraductal carcinoma of the prostate (IDC-P) is a histological subtype that differs from conventional acinar adenocarcinoma in terms of its origin, appearance, and pathological features. For IDC-P, there is currently no recognized best course of action, and its prognosis is unclear. The goal of this study is to analyze independent prognostic factors in IDC-P patients and to develop and validate a nomogram to predict overall survival (OS) and cancer-specific survival (CSS).MethodsClinical data for IDC-P patients were collected from the Surveillance, Epidemiology, and End Results database. To identify the independent variables influencing prognosis, multivariate Cox regression analysis was performed. A nomogram model was created utilizing these variables after comparing the variations in OS and CSS among various subgroups using Kaplan‒Meier curves. Internal validation of the nomograms was verified using the bootstrap resampling method.ResultsThe study included 280 IDC-P patients in total. Marital status, summary stage, grade, and the presence of lung metastases were significant factors impacting OS, and CSS was significantly influenced by marital status, summary stage, AJCC stage, the presence of lung metastases, the presence of bone metastases, and PSA according to univariate and multivariate Cox regression models (P < 0.05). Nomogram models were created to estimate OS and CSS using these parameters. The OS prediction model’s C-index was 0.744, whereas the CSS prediction model’s C-index was 0.831.ConclusionWe developed and verified nomogram models for the prediction of 1-, 3-, and 5-year OS and CSS in patients with IDC-P. These nomograms serve as a resource for evaluating patient prognosis, therapy, and diagnosis, ultimately improving clinical decision-making accuracy.

Grade group 4 prostate cancer without intraductal carcinoma on biopsy is more likely to be downgraded on prostatectomy than with intraductal carcinoma.

In this study, we investigated the association between intraductal carcinoma of the prostate (IDCP) along with several histopathological features on prostate biopsy and downgrading of grade group 4 (GG4) prostate cancer (PCa) in patients with the highest grade tumor of GG4 PCa in at least one core. A total of 29 cases had the highest grade tumor of GG4 PCa and radical prostatectomy performed between 2016 and 2021. IDCP was detected in 11 out of 29 cases on biopsy. The cases without IDCP were more likely to be downgraded on prostatectomy than with IDCP, with statistical significance (88.9% vs 36.4%, p = 0.003). The proportions of the highest-grade tumors by length and cores involved, average numbers of PCa-positive cores, and mean patient's age did not differ between cases that were downgraded and not downgraded at prostatectomy. Our results suggest that the absence of IDCP on biopsy could be a predictor of downgrading at prostatectomy for patients with the highest grade tumor of GG4 PCa.

Histological parameters and stromal desmoplastic status affecting accurate diagnosis of extraprostatic extension of prostate cancer using multi-parametric magnetic resonance imaging.

To investigate the clinicopathological factors affecting discrepancies between multi-parametric magnetic resonance imaging (mpMRI) and histopathological evaluation for diagnosis of extraprostatic extension (EPE) of prostate cancer. One hundred-and-three lesions from 96 cases with suspected EPE on preoperative mpMRI, of which 60 and 43 showed bulging and frank capsular breach, respectively, were grouped according to pathological (p)EPE in radical prostatectomy specimens. Additionally, clinicopathological/immunohistochemical findings for periostin reflecting a desmoplastic stromal reaction were compared between these groups. pEPE was detected in 49 (48%) of the 103 lesions. Of these, 25 (42%) showed bulging and 24 (56%) showed frank capsular breach on MRI. In the total cohort, the absence of pEPE was significantly associated with a lower Gleason Grade Group (GG) (p < 0.0001), anterior location (p = 0.003), absence of intraductal carcinoma of the prostate (IDC-P) (p = 0.026), and high stromal periostin expression (p < 0.0001). These trends were preserved in subgroups defined by MRI findings, except for anterior location/IDC-P in the bulging subgroup. GG, anterior location, and periostin expression may cause mpMRI-pathological discrepancies regarding EPE. Periostin expression was a significant pEPE-negative factor in all subgroup analyses. Our results indicate that patients with suspected EPE on MRI, regardless of their pEPE results, should be followed as carefully as those with definite pEPE.

Molecular complexity of intraductal carcinoma of the prostate.

Intraductal carcinoma of the prostate (IDC-P) is an aggressive subtype of prostate cancer characterized by the growth of tumor cells within the prostate ducts. It is often found alongside invasive carcinoma and is associated with poor prognosis. Understanding the molecular mechanisms driving IDC-P is crucial for improved diagnosis, prognosis, and treatment strategies. This review summarizes the molecular characteristics of IDC-P and their prognostic indications, comparing them to conventional prostate acinar adenocarcinoma, to gain insights into its unique behavior and identify potential therapeutic targets.

Abstract C090: High GLUT1 membrane expression and low PSMA membrane expression in ductal adenocarcinoma and intraductal carcinoma of the prostate

Abstract Background: Both Ductal Adenocarcinoma (DAC) and Intraductal Carcinoma (IDC) of the prostate are generally associated with aggressive clinical behavior and poor prognosis and can be lethal. Furthermore, previous studies linked aggressive clinical behavior and poor prognosis with discordant FDG positivity and low Prostate-specific membrane antigen (PSMA) expression. A recent study only cited a DAC patient with low 68Ga-PSMA-11 PET/CT uptake but high 18F-FDG PET/CT uptake, however, there is lack of directly compared articles nor large data sets. IDC-P has similar cribriform pattern in the pathological structure as a mean differential diagnosis for DAC. Hence, the objective of this study was to investigate the expression of PSMA and GLUT1 in DAC and IDC-P patients. Methods: The study was conducted on 87 DAC or IDCP patients without any treatment and 97 PAC patients with a Gleason score ≥ 8 of prostate biopsies and prostatectomy samples between August 2017 and August 2022. We performed immunohistochemical staining and scoring of various cancer component samples from the patients to reflect the protein expression levels of PSMA and GLUT1. Results: PSMA expression in PAC tissues was significantly higher than in DAC/IDC-P tissues (141.2 vs 78.6, p &amp;lt; 0.001). There was no significant difference in PSMA membrane expression between DAC/IDC-P and adjacent acinar adenocarcinoma (78.6 vs 93.4, p = 0.166). GLUT1 expression was higher in DAC/IDC-P tissue than in acinar adenocarcinoma tissue adjacent to DAC/IDC-P (68.6 vs 51.3, p = 0.007), but was still lower than that in PAC tissue (68.6 vs 93.1, p = 0.0014). It is worth noting that GLUT1 membrane expression in DAC/IDC-P was significantly increased than in PAC (13.0 vs 6.6, p = 0.025), and in acinar adenocarcinoma adjacent to DAC/IDC-P (13.0 vs 2.0, p &amp;lt; 0.001). Conclusions: In DAC and IDC-P tissues, PSMA membrane expression is low, while GLUT1 expression, especially GLUT1 membrane expression is high. These findings imply that DAC and IDC-P cells may have higher glucose metabolic and raise interest in targeting membrane GLUT1 as a novel anticancer strategy for DAC/IDC-P and other prostate cancer with high glucose metabolism. Citation Format: Xingming Wang, Xiaomei Gao, Lin Qi, Ye Zhang, Hongling Yin, Yu Gan, Yi Cai. High GLUT1 membrane expression and low PSMA membrane expression in ductal adenocarcinoma and intraductal carcinoma of the prostate [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C090.

High GLUT1 membrane expression and low PSMA membrane expression in Ductal Adenocarcinoma and Intraductal Carcinoma of the prostate.

Both Ductal Adenocarcinoma (DAC) and Intraductal Carcinoma (IDC) of the prostate are generally associated with aggressive clinical behavior and poor prognosis, which were linked with discordant FDG positivity and low Prostate-Specific Membrane Antigen (PSMA) expression. A recent study only cited a DAC patient with low 68Ga-PSMA-11 PET/CT uptake but high 18F-FDG PET/CT uptake, however, there is lack of directly compared articles nor large data sets. Hence, the objective of this study was to investigate the expression of PSMA and GLUT1 in DAC and IDC-P patients. The study was conducted on 87 DAC or/and IDC-P patients without any treatment and 97 PAC patients with a Gleason score ≥8 of prostate biopsies and prostatectomy samples between August 2017 and August 2022. We performed immunohistochemical staining and scoring of various cancer component samples from the patients to reflect the protein expression levels of PSMA and GLUT1. PSMA expression in PAC was significantly higher than in DAC/IDC-P (141.2 vs 78.6, p < 0.001). There was no significant difference in PSMA expression between DAC/IDC-P and adjacent PAC (78.6 vs 93.4, p = 0.166). GLUT1 expression was higher in DAC/IDC-P than in adjacent PAC (68.6 vs 51.3, p = 0.007), but was still lower than that in pure PAC (68.6 vs 93.1, p = 0.0014). It is worth noting that GLUT1 membrane expression in DAC/IDC-P was significantly increased than in pure PAC (13.0 vs 6.6, p = 0.025), and in PAC adjacent to DAC/IDC-P (13.0 vs 2.0, p < 0.001). In DAC/IDC-P tissues, PSMA expression is low, while GLUT1 expression, especially GLUT1 membrane expression is high. These findings imply that DAC/IDC-P may have higher glucose metabolic and raise interest in targeting membrane GLUT1 as a novel anticancer strategy for DAC/IDC-P and other prostate cancer with high glucose metabolism.

Molecular Alterations in Intraductal Carcinoma of the Prostate

Intraductal carcinoma of the prostate is most commonly associated with high-grade invasive prostate cancer. However, isolated IDC-P without adjacent cancer or high-grade cancer is also well known. Common genetic alterations present in IDC-P with adjacent high-grade prostate cancer are those described in high-grade tumors, such as PTEN loss (69–84%). In addition, the rate of LOH involving TP53 and RB1 is significantly higher. IDC-P is common in the TCGA molecular subset of SPOP mutant cancers, and the presence of SPOP mutations are more likely in IDC-P bearing tumors. IDC-P without adjacent high-grade cancers are by far less common. They are less likely to have PTEN loss (47%) and rarely harbor an ERG fusion (7%). Molecular alterations that may predispose a person to the development of IDC-P include the loss of BRCA2 and PTEN as well as mutations in SPOP. However, the causative nature of these genetic alterations is yet to be validated.

Intraductal Carcinoma of the Prostate: To Grade or Not to Grade.

Intraductal carcinoma of the prostate (IDC-P) is a distinct tumor type characterized by an expansile growth of atypical glandular epithelial cells within pre-existing prostate glands and ducts and has significant implications on clinical outcomes and patient management. There is an agreement that isolated IDC-P should not be graded, and IDC-P should be reported with a comment on its clinical significance. However, whether IDC-P should be factored into Grade Group (GG) in the presence of concurrent prostate cancer (PCa) has been debated vigorously. The contradicting opinions were promulgated when the Genitourinary Pathology Society (GUPS) and the International Society of Urological Pathologists (ISUP) published their recommendations for this issue. When IDC-P is present with PCa, the ISUP recommends incorporating it in the GG for the entire case, whereas the GUPS recommends excluding it from the final GG. Consequently, pathologists and clinicians are faced with the conundrum of conflicting recommendations. In this review article, the authors evaluate the magnitude of discrepant GG between the two grading methods, explore the rationales behind the differing views of the two urological societies, present the current reporting practices for IDC-P, and propose a provisional and pragmatic guide to alleviate the dilemma of which recommendation to follow.

Short-term prognosis of low-risk prostate cancer patients is favorable despite the presence of pathological prognostic factors: a retrospective study

BackgroundProstate cancer patients with pathological prognostic factors have a poor prognosis, but it is unclear whether pathological prognostic factors are associated with prognosis limited to low-risk patients with good prognosis according to NCCN guidelines. The present study examined whether prognosis is influenced by pathological prognostic factors using radical prostatectomy (RP) specimens from low-risk patients.MethodsWe evaluated diagnostic accuracy by examining biochemical recurrence (BCR)-free survival with respect to clinical and pathological prognostic factors in 419 all-risk patients who underwent RP. Clinical prognostic factors included age, prostate-specific antigen (PSA) levels, PSA density, and risk stratification, while pathological prognostic factors included grade group, lymphovascular space invasion, extraprostatic extension, surgical margins, seminal vesicle invasion, intraductal carcinoma of the prostate (IDCP), and pT. In a subsequent analysis restricted to 104 low-risk patients, survival curves were estimated for pathological prognostic factors using the Kaplan–Meier method and compared using log-rank and generalized Wilcoxon tests.ResultsIn the overall risk analysis, the presence of pathological prognostic factors significantly shortened BCR-free survival (p < 0.05). Univariable analysis revealed that PSA density, risk categories, and pathological prognostic factors were significantly associated with BCR-free survival, although age and PSA were not. In multivariable analysis, age, risk categories, grade group, IDCP, and pT significantly predicted BCR-free survival (p < 0.05). Conversely, no statistically significant differences were found for any pathological prognostic factors in low-risk patients.ConclusionsIn low-risk patients, pathological prognostic factors did not affect BCR-free survival, which suggests that additional treatment may be unnecessary even if pathological prognostic factors are observed in low-risk patients with RP.

Clinical Significance of Intraductal Carcinoma of the Prostate After High-Dose Brachytherapy With External Beam Radiation Therapy: A Single Institution Series and an Updated Meta-Analysis

BackgroundWe compared oncological outcomes between prostate cancer (PCa) patients with and without intraductal carcinoma of the prostate (IDC-P) after high-dose-rate brachytherapy (HDR-BT) with external beam radiation therapy (EBRT). MethodsWe performed a retrospective analysis of 138 patients with clinically high-risk, very high-risk, or locally advanced PCa who received HDR-BT with EBRT. Of these, 70 (50.7 %) patients were diagnosed with IDC-P; 68 (49.3 %) patients with acinar adenocarcinoma of prostate. The oncological outcomes, including biochemical recurrence-free survival (BCRFS) and clinical progression-free survival (CPFS), were assessed using Kaplan–Meier curves. Additionally, Cox proportional hazards models were used to identify significant prognostic indicators or biochemical recurrence (BCR). Meta-analysis of existing literatures was performed to evaluate the risk of BCR in patients with IDC-P after radiation therapy, compared to those without IDC-P. ResultsKaplan–Meier curves demonstrated significantly inferior BCRFS and CPFS in patients with IDC-P. Multivariate analysis revealed that IDC-P and Grade Group 5 status were associated with increased BCR risk. in our meta-analysis, IDC-P was associated with BCR (HR = 2.13, P = .003). ConclusionAmongst the patients who received HDR-BT, patients with IDC-P displayed significantly more rapid disease progression, compared with patients who did not have IDC-P.

Genomic and Evolutionary Characterization of Concurrent Intraductal Carcinoma and Adenocarcinoma of the Prostate.

The genomic, transcriptomic, and epigenomic characterization of concurrent intraductal carcinoma and adenocarcinoma of the prostate deepens the biological understanding of this lethal disease and provides a genetic basis for developing targeted therapies.

Distinct patterns of biomarker expression for atypical intraductal proliferations in prostate cancer.

High-grade prostatic intraepithelial neoplasia (HGPIN) is a well-characterised precursor lesion in prostate cancer. The term atypical intraductal proliferations (AIP) describes lesions with features that are far too atypical to be considered HGPIN, yet insufficient to be diagnosed as intraductal carcinoma of the prostate (IDCP). Here, a panel of biomarkers was assessed to provide insights into the biological relationship between IDCP, HGPIN, and AIP and their relevance to current clinicopathological recommendations. Tissue samples from 86 patients with prostate cancer were assessed by routine haematoxylin and eosin staining and immunohistochemistry (IHC) with a biomarker panel (Appl1/Sortilin/Syndecan-1) and a PIN4 cocktail (34βE12+P63/P504S). Appl1 strongly labelled atypical secretory cells, effectively visualising intraductal lesions. Sortilin labelling was moderate-to-strong in > 70% of cases, while Syndecan-1 was moderate-to-strong in micropapillary HGPIN/AIP lesions (83% cases) versus flat/tufting HGPIN (≤ 20% cases). Distinct biomarker labelling patterns for atypical intraductal lesions of the prostate were observed, including early atypical changes (flat/tufting HGPIN) and more advanced atypical changes (micropapillary HGPIN/AIP). Furthermore, the biomarker panel may be used as a tool to overcome the diagnostic uncertainty surrounding AIP by supporting a definitive diagnosis of IDCP for such lesions displaying the same biomarker pattern as cribriform IDCP.