Atypical intraductal proliferation and intraductal carcinoma of the prostate on core needle biopsy: a comparative clinicopathological and molecular study with a proposal to expand the morphological spectrum of intraductal carcinoma

Shah, Rajal B.; Yoon, Jiyoon; Liu, Gang; Tian, Wei

doi:10.1111/his.13273

Cited by 43 publications

(63 citation statements)

References 30 publications

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“…Table 2 summarizes the frequency of each nine epithelial features and two tumor stroma characteristics and its association with PTEN loss. Of 9 epithelial and 2 tumor stroma features of PCa analyzed, "small well-formed glands" pattern was most frequent (91%), followed by "poorly formed glands" (58%), IDC-P (31%) (Figure 1 PTEN loss observed for IDC-P in this study is consistent with that reported in previous studies analyzing the molecular features of IDC-P. 29,30 In a recent study, comparing molecular features of atypical intraductal proliferation and IDC-P in prostate biopsies, we demonstrated that PTEN loss was present in over 72% of IDC-P. 30 In addition, PTEN loss is concordant with the invasive carcinoma component in over 90% of cases. 31 Recent studies have shown that loss of cytoplasmic PTEN is associated with IDC-P, but not with HGPIN.…”

Section: Frequency Of Pten Loss Pca and Correlation With Ggsupporting

confidence: 88%

“…Of all 88 PCa cases with PTEN loss, IDC‐P was present in 61 (69%), compared to 20 (12%) of cases with intact PTEN ( P < 0.001). The high frequency of PTEN loss observed for IDC‐P in this study is consistent with that reported in previous studies analyzing the molecular features of IDC‐P . In a recent study, comparing molecular features of atypical intraductal proliferation and IDC‐P in prostate biopsies, we demonstrated that PTEN loss was present in over 72% of IDC‐P .…”

Section: Discussionmentioning

confidence: 76%

“…The high frequency of PTEN loss observed for IDC‐P in this study is consistent with that reported in previous studies analyzing the molecular features of IDC‐P . In a recent study, comparing molecular features of atypical intraductal proliferation and IDC‐P in prostate biopsies, we demonstrated that PTEN loss was present in over 72% of IDC‐P . In addition, PTEN loss is concordant with the invasive carcinoma component in over 90% of cases .…”

Section: Discussionmentioning

confidence: 86%

“…In addition, PTEN loss is concordant with the invasive carcinoma component in over 90% of cases . Recent studies have shown that loss of cytoplasmic PTEN is associated with IDC‐P, but not with HGPIN . Similar to IDC‐P, cribriform Gleason pattern 4 also showed significant association with PTEN loss.…”

Section: Discussionmentioning

confidence: 86%

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PTEN loss in prostatic adenocarcinoma correlates with specific adverse histologic features (intraductal carcinoma, cribriform Gleason pattern 4 and stromogenic carcinoma)

Shah

Shore

Yoon³

et al. 2019

The Prostate

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Background The loss of PTEN tumor suppressor gene is one of the most common somatic genetic aberrations in prostate cancer (PCa) and is frequently associated with high‐risk disease. Deletion or mutation of at least one PTEN allele has been reported to occur in 20% to 40% of localized PCa and up to 60% of metastases. The goal of this study was to determine if somatic alteration detected by PTEN immunohistochemical loss of expression is associated with specific histologic features. Methods Two hundred sixty prostate core needle biopsies with PCa were assessed for PTEN loss using an analytically validated immunohistochemical assay. Blinded to PTEN status, each tumor was assessed for the Grade Group (GG) and the presence or absence of nine epithelial features. Presence of stromogenic PCa was also assessed and defined as grade 3 reactive tumor stroma as previously described: the presence of carcinoma associated stromal response with epithelial to stroma ratio of greater than 50% reactive stroma. Results Eight‐eight (34%) cases exhibited PTEN loss while 172 (66%) had intact PTEN. PTEN loss was significantly (P < 0.05) associated with increasing GG, poorly formed glands (74% of total cases with loss vs 49% of intact), and three well‐validated unfavorable pathological features: intraductal carcinoma of the prostate (IDC‐P) (69% of total cases with loss vs 12% of intact), cribriform Gleason pattern 4 (38% of total cases with loss vs 10% of intact) and stromogenic PCa (23% of total cases with loss vs 6% of intact). IDC‐P had the highest relative risk (4.993, 95% confidence interval, 3.451‐7.223, P < 0.001) for PTEN loss. At least one of these three unfavorable pathological features were present in 67% of PCa exhibiting PTEN loss, while only 11% of PCa exhibited PTEN loss when none of these three unfavorable pathological features were present. Conclusions PCa with PTEN loss demonstrates a strong correlation with known unfavorable histologic features, particularly IDC‐P. This is the first study showing the association of PTEN loss with stromogenic PCa.

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Section: Frequency Of Pten Loss Pca and Correlation With Ggsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 86%

See 2 more Smart Citations

PTEN loss in prostatic adenocarcinoma correlates with specific adverse histologic features (intraductal carcinoma, cribriform Gleason pattern 4 and stromogenic carcinoma)

Shah

Shore

Yoon³

et al. 2019

The Prostate

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“…To our knowledge, this is the first study to report PTEN loss in RP specimens without any invasive disease (cases 3 and 4). In contrast to ERG, which is not infrequently expressed in HGPIN as an early event in PCa pathogenesis [10,45], PTEN loss is rarely observed in HGPIN, with one of our prior studies showing no PTEN loss in HGPIN lesions [20] and one study reporting PTEN loss in only one instance of HGPIN [46]. As discussed previously, PTEN loss in HGPIN occurs in the setting of retrograde spread of invasive carcinoma, but in cases without any concomitant invasive disease, no PTEN loss in HGPIN has been reported [47].…”

Section: Discussionmentioning

confidence: 67%

Intraductal carcinoma of the prostate in the absence of high‐grade invasive carcinoma represents a molecularly distinct type of in situ carcinoma enriched with oncogenic driver mutations

Khani

Wobker

Hicks

et al. 2019

The Journal of Pathology

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Intraductal carcinoma of the prostate (IDC‐P) most often appears associated with high‐grade invasive prostate carcinoma (PCa), where it is believed to represent retrograde spread. However, IDC‐P rarely occurs as an isolated finding at radical prostatectomy or with concurrent low‐grade (Grade Group 1) invasive carcinoma. We hypothesized that isolated IDC‐P (iIDC‐P) in these unusual cases may represent a distinct in situ lesion and molecularly profiled 15 cases. iIDC‐P was characterized by copy number alteration (CNA) profiling and targeted next generation sequencing in cases with sufficient tissue (n = 7). Immunohistochemistry for PTEN and ERG was performed on the total cohort (n = 15), where areas of iIDC‐P and associated invasive disease were evaluated separately (n = 9). By copy number profiling, iIDC‐P alterations were similar to those previously described in high‐grade invasive PCa (PTEN, RB1, and CHD1 loss; MYC gain). However, in four cases, targeted sequencing revealed a striking number of activating oncogenic driver mutations in MAPK and PI3K pathway genes, which are extraordinarily rare in conventional PCa. In addition, pathogenic mutations in DNA repair genes were found in two cases of iIDC‐P (BRCA2, CHEK2, CDK12) and other known PCa‐associated mutations (FOXA1, SPOP) in two cases. Overall, ERG was expressed in 7% (1/15) of the iIDC‐P lesions and PTEN was lost in 53% (8/15). Discordance for ERG or PTEN status between IDC‐P and the low‐grade PCa was observed in five of nine cases, with intact PTEN in the invasive tumor and PTEN loss in IDC‐P in four. Despite a CNA profile similar to conventional PCa, iIDC‐P is enriched with potentially targetable oncogenic driver mutations in MAPK/PI3K genes. Based on PTEN and ERG status, iIDC‐P is not likely a precursor to the associated low‐grade invasive PCa, but represents a molecularly unique in situ tumor of unclear clinical significance. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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Is high‐grade prostatic intraepithelial neoplasia (HGPIN) a reliable precursor for prostate carcinoma? Implications for clonal evolution and early detection strategies

Tolkach

Kristiansen

2018

The Journal of Pathology

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High-grade prostatic intraepithelial neoplasia (HGPIN) is a documented putative precursor lesion for invasive prostate adenocarcinoma. However, the precise mechanisms of the carcinoma's development from HGPIN are unclear. Many studies have attempted a comparative molecular genetic characterisation of HGPIN and its corresponding carcinoma to study this transformation. However, to date, some HGPIN mimickers, such as intraductal carcinoma, which can engage in retrograde colonisation of the prostatic acini in an HGPIN-like manner, have been described. In this work, we hypothesise that the lesion formerly known as HGPIN adjacent to invasive carcinoma does not necessarily represent its respective precursor lesion. This hypothesis stems from recent morphological, experimental, and theoretical evidence on the development of tumour clonality, as well as recent studies outlining the three-dimensional architecture of prostate adenocarcinomas (most importantly, their interconnection with the tumoural glandular system). Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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Atypical intraductal proliferation and intraductal carcinoma of the prostate on core needle biopsy: a comparative clinicopathological and molecular study with a proposal to expand the morphological spectrum of intraductal carcinoma

Abstract: AIP represents a lower-grade morphological spectrum of IDC-P, associated with intermediate-risk PCa. Patients with only AIP need an immediate repeat biopsy to rule out clinically significant PCa.

Cited by 43 publications

References 30 publications

PTEN loss in prostatic adenocarcinoma correlates with specific adverse histologic features (intraductal carcinoma, cribriform Gleason pattern 4 and stromogenic carcinoma)

PTEN loss in prostatic adenocarcinoma correlates with specific adverse histologic features (intraductal carcinoma, cribriform Gleason pattern 4 and stromogenic carcinoma)

Intraductal carcinoma of the prostate in the absence of high‐grade invasive carcinoma represents a molecularly distinct type of in situ carcinoma enriched with oncogenic driver mutations

Is high‐grade prostatic intraepithelial neoplasia (HGPIN) a reliable precursor for prostate carcinoma? Implications for clonal evolution and early detection strategies

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