Intraductal carcinoma of the prostate| Pathologica - Journal of the Italian Society of Anatomic Pathology and Diagnostic Cytopathology
Vol. 112 No. 1 (2020): Pathologica - Issue 1 - March 2020
DOI: 10.32074/1591-951X-5-20
Review
Published: 2020-03-12
download
PDF

Intraductal carcinoma of the prostate

Vanderbilt University Medical Center, Nashville, USA
Vanderbilt University Medical Center, Nashville, USA

Abstract

Intraductal carcinoma of the prostate (IDC-P) is a diagnostic entity characterized by architecturally or cytologically malignant-appearing prostatic glandular epithelium confined to prostatic ducts. Despite its apparent in situ nature, this lesion is associated with aggressive prostatic adenocarcinoma and is a predictor for poor prognosis when identified on biopsy or radical prostatectomy. This review discusses diagnosis, clinical features, histogenesis, and management of IDC-P, as well as current research and controversies surrounding this entity.

Introduction

Despite its apparent in situ nature, intraductal carcinoma of the prostate (IDC-P) is associated with aggressive behavior and poor outcome. While this may appear counterintuitive, current theories on histogenesis of IDC-P suggest that many of these lesions represent adenocarcinoma with retrograde invasion into the prostatic ducts 1. Thus, most IDC-P are not biologically or pathologically distinct from conventional prostatic adenocarcinoma but rather a morphologic manifestation of the aggressive nature of the underlying cancer. An overview of the clinical and pathological features of IDC-P will be provided herein with an emphasis on current research and controversies regarding this entity.

Epidemiology and diagnostic criteria

First described in an autopsy study in 1938 2, IDC-P became more widely studied in the mid-1980’s with the increasing use of immunohistochemistry 3,4. Diagnostic criteria for IDC-P were first proposed by Guo and Epstein in 2006 (Tab. I, Fig. 1A-1D) and subsequently endorsed by the World Health Organization (WHO) tumor classification, which recognized IDC-P as a distinct entity in 2016 5,6. The WHO defines IDC-P as an “intra-acinar and/or intraductal neoplastic epithelial proliferation that has some features of high grade prostatic intraepithelial neoplasia (HGPIN) but exhibits much greater architectural and/or cytological atypia, typically associated with high grade or high stage prostate carcinoma” 6.

The prevalence of IDC-P is largely dependent on the patient cohort, ranging from 2-3% in low-risk or overall patient cohorts 7,8 to 67% in metastatic/recurrent disease 8-10 for biopsy specimens, and 13-17% in radical prostatectomy (RP) specimens 11,12.

Lesions that do not meet morphologic criteria for IDC-P but appear more complex than HGPIN either architecturally or cytologically have been termed “atypical intraductal proliferations” (AIP) 13-15 (Tab. I, Fig. 1E-F).

Clinical features and reporting recommendations

IDC-P is independently associated with adverse clinical and pathological features on both biopsy and RP. Specifically, RP studies have shown that patients with IDC-P have higher pathologic T stage 10,16-18, higher Gleason score 10,16-20, increased tumor volume 3,4,10,16-19, and increased likelihood of extraprostatic extension 5,10,16,20, seminal vesicle invasion 10,19, and lymph node metastases 10,20. These patients also have an increased risk of biochemical recurrence 21,22 and metastasis 22 and worse progression-free, cancer-specific, and overall survival 10,20.

Patients with IDC-P detected on biopsy have higher Gleason score and likelihood of seminal vesicle invasion on RP 7 as well as worse progression-free, cancer-specific, and overall survival 23-25. While the finding of IDC-P on biopsy is highly specific for detection of IDC-P on RP, the sensitivity is relatively low (56.5% overall and 34.1% for active surveillance cohorts), making a positive finding more prognostically valuable than a negative one 26.

In the setting of metastatic disease, patients with IDC-P show worse cancer-specific and overall survival 23,27,28 and increased likelihood of development of castration-resistant prostate cancer (CRPC) 28. In metastatic CRPC, IDC-P is a predictor of decreased cancer-specific and overall survival 29-31 as well as early relapse following neoadjuvant chemotherapy 32, relapse following androgen deprivation therapy 33 and radiation therapy 9. IDC-P is also highly prevalent after androgen deprivation therapy or chemotherapy (60%) 8.

There is some heterogeneity in outcomes reported with different patterns of IDC-P. Solid and dense cribriform patterns are prognostically more unfavorable than loose cribriform or micropapillary patterns in localized 19 and metastatic disease 27.

While conventional IDC-P represents retrograde spread of invasive high grade carcinoma and is associated with aggressive features at RP, studies have suggested that isolated IDC-P or IDC-P with low grade adenocarcinoma may represent a precursor, de novo lesion associated with better clinical outcome 34-36. The former category is termed “regular type” IDC-P, as opposed to “precursor-like” IDC-P, which is considered a precursor to invasive adenocarcinoma 34. These two entities are currently pathologically indistinguishable. Isolated IDC-P, i.e., IDC-P without concurrent invasive carcinoma is found in 0.1-0.3% of biopsies 7,35.

Lesions diagnosed as AIP have clinical features more similar to IDC-P than to HGPIN. Patients with AIP and IDC-P on needle biopsy do not have a significantly different incidence of associated invasive carcinoma, although invasive carcinoma associated with IDC-P has higher Gleason score and higher percentage of needle core involvement on biopsy 15. Patients with a diagnosis of AIP without associated prostate cancer on needle core biopsy have a 50% likelihood of a subsequent diagnosis of invasive carcinoma or IDC-P 13. On RP, patients with invasive carcinoma and AIP or IDC-P have similar clinicopathologic characteristics, including no significant difference in Gleason score, tumor stage, seminal vesicle invasion, and surgical margins 11,12. Patients with AIP carry an intermediate risk of biochemical recurrence between those with IDC-P and HGPIN 12.

There is significant controversy as to whether IDC-P should be included in the Grade Group system. Based on recent studies showing that IDC-P/cribriform architecture is a poor prognostic factor independent of Grade Group 37,38, some groups advocate its incorporation into the Grade Group system 37,39. However, in view of the limited evidence on the association of IDC-P with low-grade invasive carcinoma, as well as the overlapping morphology of precursor-like and regular type IDC-P, some authors argue against incorporating IDC-P into the Grade Group system 40. Furthermore, precursor-like and isolated IDC-P have a different expression pattern of PTEN and ERG from the concurrent low-grade cancer, suggesting that isolated IDC-P is unrelated to the associated low-grade invasive prostate cancer 41. Currently, the European Association of Urology (EAU) guidelines do not support assigning a grade to IDC-P and recommend reporting IDC-P separately from Grade Group 42.

Differential diagnosis

IDC-P shares morphologic features with several entities. HGPIN is a precursor for prostatic adenocarcinoma and its diagnosis on biopsy (if unifocal, i.e. limited to one core) does not increase the risk of carcinoma detection on repeat biopsy 43,44. Similarly to IDC-P, HGPIN consists of cytologically malignant cells confined to ducts or acini; however, HGPIN will not demonstrate the same degree of cellular density, architectural and cytologic atypia, or necrosis that are typical of IDC-P (Tab. I, Fig. 1A-1D). In practice, especially in the setting of limited tissue, this distinction is not straightforward, as some IDC-P can have a low-grade appearance 45. Both IDC-P and HGPIN have preservation of basal cells and both express AMACR by immunohistochemistry. Immunohistochemical ERG expression or PTEN loss may be helpful to support a diagnosis of IDC-P in this context, as these features are not typical of HGPIN 13,46-48 (Fig. 2).

The distinction between IDC-P and invasive acinar adenocarcinoma (cribriform Gleason pattern 4 or solid Gleason pattern 5) can be challenging on H&E sections, but it can be easily resolved by immunohistochemistry with the former displaying basal cell staining and the latter having complete loss of basal cells. Given that IDC-P is confined by ducts, these will have smoother contours, well circumscribed borders and follow a more organized branching architecture 5. The presence of comedonecrosis strongly suggests a diagnosis of IDC-P 49, while perineural invasion or extraprostatic extension favor invasive carcinoma 50,51. As both entities represent high grade malignancy, clinical management is similar 52,53.

Despite similarities in nomenclature, IDC-P and ductal adenocarcinoma have distinct morphologies. Ductal adenocarcinoma is characterized by tall pseudostratified columnar cells commonly forming true papillae with fibrovascular cores and sometimes displaying cribriform architecture. IDC-P has cuboidal (acinar) cells, can display micropapillary architecture without fibrovascular cores, and has a greater degree of cytologic atypia. Notably, ductal adenocarcinoma can occasionally involve the ducts and demonstrate persistence of basal cell markers. In these cases, a diagnosis of “intraductal carcinoma with ductal features” is rendered. Ductal adenocarcinoma is graded as Gleason pattern 4 6.

Urothelial carcinoma involving prostatic ducts can sometimes be challenging to distinguish from the solid pattern of IDC-P on H&E. Extreme pleomorphism, high mitotic activity or apoptosis, and dense eosinophilic cytoplasm are morphologic features that favor urothelial carcinoma, while any glandular differentiation favors IDC-P. Fortunately, these entities are easily distinguishable by immunohistochemical markers as IDC-P will stain with prostatic markers, e.g. PSA, PSAP, p501s, and NKX3.1, while urothelial carcinoma will stain with HMWCK, p63, and GATA3. This distinction is important for management, as urothelial carcinoma involving prostatic ducts will be managed with radical cystoprostatectomy 43,52.

Molecular features and histogenesis

The most common early molecular aberration in prostatic adenocarcinoma is the fusion between the androgen regulated serine protease TMPRSS2 and members of the ETS transcription factor family, most commonly ERG, driving overexpression of the ERG oncogene 54-56. This rearrangement is mutually exclusive with other early driver mutations such as those involving SPOP. The prognostic significance of the TMPRSS2-ERG rearrangement is unclear 57-61. Additional second line genetic alterations, all associated with more aggressive disease, include PTEN, TP53, RB1, MYC, and BRCA2 54,62,63. Of these, PTEN loss has been the most studied and has been shown to be significantly associated with high Gleason grade, advanced tumor stage, and decreased time to metastasis 64,65. Large scale genomic alterations, including copy number alterations, deletions, gains, and fusions comprise the majority of genetic alterations in prostate cancer.

IDC-P predominantly shows TMPRSS2-ERG fusion as an early driver mutation and has numerous second line genetic alterations associated with aggressive and metastatic disease (Fig. 2). Of note, HGPIN harbors the TMPRSS2-ERG fusion as well as PTEN loss much less frequently 10,66-69, while prevalence of these alterations in AIP is more similar to that seen in IDC-P 48,70. Loss of heterozygosity (LOH), chromosomal imbalances, and percent genomic alteration have been found to be significantly higher in IDC-P compared with invasive prostate carcinoma and much higher than those seen in HGPIN 22,71-73.

Patients with germline mutations in genes associated with DNA repair (most commonly BRCA2, ATM, CHEK2, BRCA1) and BRCA2 specifically have been found to have a higher incidence of IDC-P 74-76, prompting recommendations for germline genetic testing in patients with this diagnosis even in the absence of family history 77.

Molecular findings also provide evidence for the histogenesis of IDC-P. Intraductal carcinoma and adjacent acinar adenocarcinoma share the same TMPRSS2-ERG genomic breakpoints, supporting the idea of a common clonal origin 1,78. Additionally, invasive carcinoma adjacent to IDC-P with PTEN loss also shows similar PTEN abnormality, suggesting that IDC-P represents retrograde colonization of ducts by a subclone of an invasive carcinoma. The aggressiveness of this subclone is highlighted by the presence of similar copy number alteration patterns in IDC-P and metastasis 79.

Molecular findings also provide evidence for the distinction between regular type and precursor-like IDC-P. A subset of isolated IDC-P showed molecular alterations in the MAPK/PI3K pathway that are distinct from those of regular type IDC-P and conventional acinar adenocarcinoma 41. This heterogeneity in IDC-P makes its categorization and clinical ramifications difficult and requires further research.

Management

There is no consensus on the management of IDC-P. Given the association of IDC-P with high grade and high volume invasive carcinoma on RP, the majority of authors recommend definitive therapy or suggest immediate re-biopsy when IDC-P is diagnosed. This is true even in the absence of invasive carcinoma 5,18,35,52 or with low grade, Gleason 3 + 3 = 6 carcinoma 36,52. Because AIP on biopsy is associated with an increased risk of invasive carcinoma or IDC-P 13,48, this diagnosis warrants immediate re-biopsy 15. Reporting IDC-P on radical prostatectomy is useful for prognostic purposes and for recommendation of germline testing; otherwise, clinical management is decided on a case by case basis 52,77.

Conclusions

IDC-P is associated with aggressive prostate cancer, early biochemical recurrence, and decreased survival. Diagnosis and early reporting are paramount for patient management due to significant therapeutic and prognostic implications. Further studies are needed to address current unresolved issues and fully understand the biological nature of this entity.

Figures and tables

Figure 1.Intraductal carcinoma of the prostate (IDC-P) and atypical intraductal proliferation (AIP): (A) Solid pattern of IDC-P (Original magnification ×40); (B) Nuclei 6x larger than those of adjacent benign cells (Original magnification ×200); (C) Dense cribriform pattern with comedonecrosis (Original magnification ×100); (D) Preserved basal cell staining by immunohistochemistry for p63 (Original magnification ×100). (E) Loose cribriform pattern with lack of pleomorphism and comedonecrosis in AIP (Original magnification ×100); (F) Preserved basal cell staining and AMACR positivity in AIP (Triple stain with p63, HMWCK and AMACR) (Original magnification ×40).

Figure 2.Molecular alterations in intraductal carcinoma (highlighted in bold) and invasive carcinoma of the prostate.

Intraductal carcinoma of the prostate Atypical intraductal proliferation
Malignant epithelial cells filling large acini and prostatic ducts Solid or dense cribriform pattern with cellular density > 50% of luminal space Loose cribriform or micropapillary pattern with either Marked nuclear atypia with nuclei at least 6x larger than adjacent benign nuclei or Nonfocal comedonecrosis Preservation of basal cells Malignant epithelial cells filling large acini and prostatic ducts Solid or dense cribriform pattern incompletely spanning the lumen with cellular density < 50% of luminal space Loose cribriform or micropapillary pattern with both Insufficient nuclear pleomorphism to meet diagnostic criteria for IDC-P Absence of necrosis Preservation of basal cells
Tab. I.Diagnostic criteria for IDC-P (left panel) and AIP (right panel). Adapted from Guo & Epstein 2006 5 and Shah et al. 2017 15.

References

  1. Haffner MC, Weier C, Xu MM. Molecular evidence that invasive adenocarcinoma can mimic prostatic intraepithelial neoplasia (PIN) and intraductal carcinoma through retrograde glandular colonization. J Pathol. 2016; 238:31-41. DOI
  2. Gaynor EP. Zur Frage des Prostatakrebses. Virchows Arch. 1938; 301:602-52. DOI
  3. Kovi J, Jackson MA, Heshmat MY. Ductal spread in prostatic carcinoma. Cancer. 1985; 56:1566-73. DOI
  4. McNeal JE, Reese JH, Redwine EA. Cribriform adenocarcinoma of the prostate. Cancer. 1986; 58:1714-9. DOI
  5. Guo CC, Epstein JI. Intraductal carcinoma of the prostate on needle biopsy: Histologic features and clinical significance. Mod Pathol. 2006; 19:1528-35. DOI
  6. Moch H HP, Ulbright TM, Reuter V.. IAfRo Cancer. Lyon, France.
  7. Watts K, Li J, Magi-Galluzzi C. Incidence and clinicopathological characteristics of intraductal carcinoma detected in prostate biopsies: a prospective cohort study. Histopathology. 2013; 63:574-9. DOI
  8. Porter LH, Lawrence MG, Ilic D. Systematic Review Links the Prevalence of Intraductal Carcinoma of the Prostate to Prostate Cancer Risk Categories. Eur Urol. 2017; 72:492-95. DOI
  9. Van der Kwast T, Al Daoud N, Collette L. Biopsy diagnosis of intraductal carcinoma is prognostic in intermediate and high risk prostate cancer patients treated by radiotherapy. Eur J Cancer. 2012; 48:1318-25. DOI
  10. Kimura K, Tsuzuki T, Kato M. Prognostic value of intraductal carcinoma of the prostate in radical prostatectomy specimens. Prostate. 2014; 74:680-7. DOI
  11. Han B, Suleman K, Wang L. ETS gene aberrations in atypical cribriform lesions of the prostate: Implications for the distinction between intraductal carcinoma of the prostate and cribriform high-grade prostatic intraepithelial neoplasia. Am J Surg Pathol. 2010; 34:478-85. DOI
  12. Miyai K, Divatia MK, Shen SS. Clinicopathological analysis of intraductal proliferative lesions of prostate: intraductal carcinoma of prostate, high-grade prostatic intraepithelial neoplasia, and atypical cribriform lesion. Hum Pathol. 2014; 45:1572-81. DOI
  13. Morais CL, Han JS, Gordetsky J. Utility of PTEN and ERG immunostaining for distinguishing high-grade PIN from intraductal carcinoma of the prostate on needle biopsy. Am J Surg Pathol. 2015; 39:169-78. DOI
  14. Shah RB, Magi-Galluzzi C, Han B. Atypical cribriform lesions of the prostate: relationship to prostatic carcinoma and implication for diagnosis in prostate biopsies. Am J Surg Pathol. 2010; 34:470-7. DOI
  15. Shah RB, Yoon J, Liu G. 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. Histopathology. 2017; 71:693-702. DOI
  16. Rubin MA, de La Taille A, Bagiella E. Cribriform carcinoma of the prostate and cribriform prostatic intraepithelial neoplasia: incidence and clinical implications. Am J Surg Pathol. 1998; 22:840-8. DOI
  17. Cohen RJ, Chan WC, Edgar SG. Prediction of pathological stage and clinical outcome in prostate cancer: an improved pre-operative model incorporating biopsy-determined intraductal carcinoma. Br J Urol. 1998; 81:413-8. DOI
  18. Cohen RJ, Wheeler TM, Bonkhoff H. A proposal on the identification, histologic reporting, and implications of intraductal prostatic carcinoma. Arch Pathol Lab Med. 2007; 131:1103-9.
  19. Wilcox G, Soh S, Chakraborty S. Patterns of high-grade prostatic intraepithelial neoplasia associated with clinically aggressive prostate cancer. Hum Pathol. 1998; 29:1119-23. DOI
  20. Dinerman BF, Khani F, Golan R. Population-based study of the incidence and survival for intraductal carcinoma of the prostate. Urol Oncol. 2017; 35:673. DOI
  21. O’Brien BA, Cohen RJ, Wheeler TM. A post-radical-prostatectomy nomogram incorporating new pathological variables and interaction terms for improved prognosis. BJU Int. 2011; 107:389-95. DOI
  22. Chua MLK, Lo W, Pintilie M. A Prostate Cancer “Nimbosus”: Genomic Instability and SChLAP1 Dysregulation Underpin Aggression of Intraductal and Cribriform Subpathologies. Eur Urol. 2017; 72:665-74. DOI
  23. Kato M, Kimura K, Hirakawa A. Prognostic parameter for high risk prostate cancer patients at initial presentation. Prostate. 2018; 78:11-16. DOI
  24. Kweldam CF, Kummerlin IP, Nieboer D. Disease-specific survival of patients with invasive cribriform and intraductal prostate cancer at diagnostic biopsy. Mod Pathol. 2016; 29:630-6. DOI
  25. Saeter T, Vlatkovic L, Waaler G. Intraductal Carcinoma of the Prostate on Diagnostic Needle Biopsy Predicts Prostate Cancer Mortality: A Population-Based Study. Prostate. 2017; 77:859-65. DOI
  26. Ericson KJ, Wu S, Lundy SD. Diagnostic Accuracy of Prostate Biopsy for Detecting Cribriform Gleason Pattern 4 Carcinoma and Intraductal Carcinoma in Paired Radical Prostatectomy Specimens: Implications for Active Surveillance. J Urol. 2019;101097JU0000000000000526. DOI
  27. Zhao J, Liu J, Sun G. The Prognostic Value of the Proportion and Architectural Patterns of Intraductal Carcinoma of the Prostate in Patients with De Novo Metastatic Prostate Cancer. J Urol. 2019; 201:759-68. DOI
  28. Zhao T, Liao B, Yao J. Is there any prognostic impact of intraductal carcinoma of prostate in initial diagnosed aggressively metastatic prostate cancer?. Prostate. 2015; 75:225-32. DOI
  29. Yamamoto A, Kato M, Matsui H. Efficacy of docetaxel in castration-resistant prostate cancer patients with intraductal carcinoma of the prostate. Int J Clin Oncol. 2018; 23:584-90. DOI
  30. Chen Z, Chen N, Shen P. The presence and clinical implication of intraductal carcinoma of prostate in metastatic castration resistant prostate cancer. Prostate. 2015; 75:1247-54. DOI
  31. Zhao J, Shen P, Sun G. The prognostic implication of intraductal carcinoma of the prostate in metastatic castration-resistant prostate cancer and its potential predictive value in those treated with docetaxel or abiraterone as first-line therapy. Oncotarget. 2017; 8:55374-83. DOI
  32. O’Brien C, True LD, Higano CS. Histologic changes associated with neoadjuvant chemotherapy are predictive of nodal metastases in patients with high-risk prostate cancer. Am J Clin Pathol. 2010; 133:654-61. DOI
  33. Efstathiou E, Abrahams NA, Tibbs RF. Morphologic characterization of preoperatively treated prostate cancer: toward a post-therapy histologic classification. Eur Urol. 2010; 57:1030-8. DOI
  34. Miyai K, Divatia MK, Shen SS. Heterogeneous clinicopathological features of intraductal carcinoma of the prostate: a comparison between “precursor-like” and “regular type” lesions. Int J Clin Exp Pathol. 2014; 7:2518-26.
  35. Robinson BD, Epstein JI. Intraductal carcinoma of the prostate without invasive carcinoma on needle biopsy: emphasis on radical prostatectomy findings. J Urol. 2010; 184:1328-33. DOI
  36. Khani F, Epstein JI. Prostate Biopsy Specimens With Gleason 3+3=6 and Intraductal Carcinoma: Radical Prostatectomy Findings and Clinical Outcomes. Am J Surg Pathol. 2015; 39:1383-9. DOI
  37. Kato M, Hirakawa A, Kobayashi YM. The influence of the presence of intraductal carcinoma of the prostate on the grade group system’s prognostic performance. Prostate. 2019; 79:1065-70. DOI
  38. Kweldam CF, van Leenders GJ, van der Kwast T. Grading of prostate cancer: a work in progress. Histopathology. 2019; 74:146-60. DOI
  39. van Leenders G, Kweldam CF, Hollemans E. Improved Prostate Cancer Biopsy Grading by Incorporation of Invasive Cribriform and Intraductal Carcinoma in the 2014 Grade Groups. Eur Urol. 2019. DOI
  40. Epstein JI. Is There Enough Support for a New Prostate Grading System Factoring in Intraductal Carcinoma and Cribriform Cancer?. Eur Urol. 2019. DOI
  41. Khani F, Wobker SE, Hicks JL. 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. J Pathol. 2019; 249:79-89. DOI
  42. Mottet N BJ, Briers E, Bolla M, Bourke L, Cornford P, De Santis M, Henry A, Joniau S, Lam T, Mason MD, Van den Poel H, Van den Kwast TH, Rouvière O, Wiegel T, members of the EAU – ESTRO – ESUR –SIOG Prostate Cancer Guidelines Panel. EAU – ESTRO – ESUR – SIOG Guidelines on Prostate Cancer.Publisher Full Text
  43. Wobker SE, Epstein JI. Differential Diagnosis of Intraductal Lesions of the Prostate. Am J Surg Pathol. 2016; 40:e67-82. DOI
  44. Epstein JI NG. Biopsy interpretation of the prostate. WKHA (ESP). 2014.
  45. Zhou M. Intraductal carcinoma of the prostate: the whole story. Pathology. 2013; 45:533-9. DOI
  46. Shah RB, Zhou M. Atypical cribriform lesions of the prostate: clinical significance, differential diagnosis and current concept of intraductal carcinoma of the prostate. Adv Anat Pathol. 2012; 19:270-8. DOI
  47. Lotan TL, Gumuskaya B, Rahimi H. Cytoplasmic PTEN protein loss distinguishes intraductal carcinoma of the prostate from high-grade prostatic intraepithelial neoplasia. Mod Pathol. 2013; 26:587-603. DOI
  48. Shah RB, Shore KT, Yoon J. PTEN loss in prostatic adenocarcinoma correlates with specific adverse histologic features (intraductal carcinoma, cribriform Gleason pattern 4 and stromogenic carcinoma). Prostate. 2019; 79:1267-73. DOI
  49. Fine SW, Al-Ahmadie HA, Chen YB. Comedonecrosis Revisited: Strong Association With Intraductal Carcinoma of the Prostate. Am J Surg Pathol. 2018; 42:1036-41. DOI
  50. Kronz JD, Shaikh AA, Epstein JI. Atypical cribriform lesions on prostate biopsy. Am J Surg Pathol. 2001; 25:147-55. DOI
  51. Epstein JI. Mimickers of prostatic intraepithelial neoplasia. Int J Surg Pathol. 2010; 18:142S-48S. DOI
  52. Magers M, Kunju LP, Wu A. Intraductal Carcinoma of the Prostate: Morphologic Features, Differential Diagnoses, Significance, and Reporting Practices. Arch Pathol Lab Med. 2015; 139:1234-41. DOI
  53. Divatia MK, Ro JY. Intraductal Carcinoma of the Prostate Gland: Recent Advances. Yonsei Med J. 2016; 57:1054-62. DOI
  54. Arora K, Barbieri CE. Molecular Subtypes of Prostate Cancer. Curr Oncol Rep. 2018; 20:58. DOI
  55. Tomlins SA, Rhodes DR, Perner S. Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science. 2005; 310:644-8. DOI
  56. Tomlins SA, Bjartell A, Chinnaiyan AM. ETS gene fusions in prostate cancer: from discovery to daily clinical practice. Eur Urol. 2009; 56:275-86. DOI
  57. Wang J, Cai Y, Ren C. Expression of variant TMPRSS2/ERG fusion messenger RNAs is associated with aggressive prostate cancer. Cancer Res. 2006; 66:8347-51. DOI
  58. Rajput AB, Miller MA, De Luca A. Frequency of the TMPRSS2:ERG gene fusion is increased in moderate to poorly differentiated prostate cancers. J Clin Pathol. 2007; 60:1238-43. DOI
  59. Nam RK, Sugar L, Wang Z. Expression of TMPRSS2:ERG gene fusion in prostate cancer cells is an important prognostic factor for cancer progression. Cancer Biol Ther. 2007; 6:40-5. DOI
  60. Gopalan A, Leversha MA, Satagopan JM. TMPRSS2-ERG gene fusion is not associated with outcome in patients treated by prostatectomy. Cancer Res. 2009; 69:1400-6. DOI
  61. Pettersson A, Graff RE, Bauer SR. The TMPRSS2:ERG rearrangement, ERG expression, and prostate cancer outcomes: a cohort study and meta-analysis. Cancer Epidemiol Biomarkers Prev. 2012; 21:1497-509. DOI
  62. Cancer Genome Atlas Research N. The Molecular Taxonomy of Primary Prostate Cancer. Cell. 2015; 163:1011-25. DOI
  63. Robinson D, Van Allen EM, Wu YM. Integrative Clinical Genomics of Advanced Prostate Cancer. Cell. 2015; 162:454. DOI
  64. Krohn A, Diedler T, Burkhardt L. Genomic deletion of PTEN is associated with tumor progression and early PSA recurrence in ERG fusion-positive and fusion-negative prostate cancer. Am J Pathol. 2012; 181:401-12. DOI
  65. Lotan TL, Gurel B, Sutcliffe S. PTEN protein loss by immunostaining: analytic validation and prognostic indicator for a high risk surgical cohort of prostate cancer patients. Clin Cancer Res. 2011; 17:6563-73. DOI
  66. Cerveira N, Ribeiro FR, Peixoto A. TMPRSS2-ERG gene fusion causing ERG overexpression precedes chromosome copy number changes in prostate carcinomas and paired HGPIN lesions. Neoplasia. 2006; 8:826-32. DOI
  67. Mosquera JM, Perner S, Genega EM. Characterization of TMPRSS2-ERG fusion high-grade prostatic intraepithelial neoplasia and potential clinical implications. Clin Cancer Res. 2008; 14:3380-5. DOI
  68. Perner S, Mosquera JM, Demichelis F. TMPRSS2-ERG fusion prostate cancer: an early molecular event associated with invasion. Am J Surg Pathol. 2007; 31:882-8. DOI
  69. Yoshimoto M, Cutz JC, Nuin PA. Interphase FISH analysis of PTEN in histologic sections shows genomic deletions in 68% of primary prostate cancer and 23% of high-grade prostatic intra-epithelial neoplasias. Cancer Genet Cytogenet. 2006; 169:128-37. DOI
  70. Morais CL, Guedes LB, Hicks J. ERG and PTEN status of isolated high-grade PIN occurring in cystoprostatectomy specimens without invasive prostatic adenocarcinoma. Hum Pathol. 2016; 55:117-25. DOI
  71. Dawkins HJ, Sellner LN, Turbett GR. Distinction between intraductal carcinoma of the prostate (IDC-P), high-grade dysplasia (PIN), and invasive prostatic adenocarcinoma, using molecular markers of cancer progression. Prostate. 2000; 44:265-70. DOI
  72. Bettendorf O, Schmidt H, Staebler A. Chromosomal imbalances, loss of heterozygosity, and immunohistochemical expression of TP53, RB1, and PTEN in intraductal cancer, intraepithelial neoplasia, and invasive adenocarcinoma of the prostate. Genes Chromosomes Cancer. 2008; 47:565-72. DOI
  73. Bottcher R, Kweldam CF, Livingstone J. Cribriform and intraductal prostate cancer are associated with increased genomic instability and distinct genomic alterations. BMC Cancer. 2018; 18:8. DOI
  74. Risbridger GP, Taylor RA, Clouston D. Patient-derived xenografts reveal that intraductal carcinoma of the prostate is a prominent pathology in BRCA2 mutation carriers with prostate cancer and correlates with poor prognosis. Eur Urol. 2015; 67:496-503. DOI
  75. Taylor RA, Fraser M, Livingstone J. Germline BRCA2 mutations drive prostate cancers with distinct evolutionary trajectories. Nat Commun. 2017; 8:13671. DOI
  76. Isaacsson Velho P, Silberstein JL, Markowski MC. Intraductal/ductal histology and lymphovascular invasion are associated with germline DNA-repair gene mutations in prostate cancer. Prostate. 2018; 78:401-07. DOI
  77. Network NCC. Prostate cancer (version 4.2019). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). 2019. Publisher Full Text
  78. Schneider TM, Osunkoya AO. ERG expression in intraductal carcinoma of the prostate: comparison with adjacent invasive prostatic adenocarcinoma. Mod Pathol. 2014; 27:1174-8. DOI
  79. Lindberg J, Kristiansen A, Wiklund P. Tracking the origin of metastatic prostate cancer. Eur Urol. 2015; 67:819-22. DOI

Affiliations

$authorString->getOrcid() =>

$authorString->getFullName() => Eszter Szentirmai

$authorString->getUrl() =>

Eszter Szentirmai

Vanderbilt University Medical Center, Nashville, USA
non esiste orcidID ""

$authorString->getOrcid() =>

$authorString->getFullName() => Giovanna Angela Giannico

$authorString->getUrl() =>

Giovanna Angela Giannico

Vanderbilt University Medical Center, Nashville, USA
non esiste orcidID ""

License

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Copyright

© Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathology , 2020

How to Cite

[1]
Szentirmai, E. and Giannico, G.A. 2020. Intraductal carcinoma of the prostate. Pathologica - Journal of the Italian Society of Anatomic Pathology and Diagnostic Cytopathology. 112, 1 (Mar. 2020), 17-24. DOI:https://doi.org/10.32074/1591-951X-5-20.
  • Abstract viewed - 4243 times
  • PDF downloaded - 1331 times