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Reactive stroma and acinar morphology in prostate cancer: implications for progression and prognostic assessment

Reactive stroma and acinar morphology in prostate cancer: implications for progression and prognostic assessment
Reactive stroma and acinar morphology in prostate cancer: implications for progression and prognostic assessment

Introduction: prostate cancer (PC) remains a significant global health concern, with prognostic assessments largely reliant on the Gleason Classification System. While it has proven effective, subjectivity in interpretation persists, prompting the need for complementary approaches. Reactive stroma (RS) has emerged as a potential candidate for enhancing PC characterization, as it reflects intricate interactions among stromal, epithelial, and extracellular matrix components. To shed light on this, we conducted a comprehensive study. 

Methods: two expert pathologists independently analyzed consecutive prostate biopsies (n = 120 patients), categorized into four groups based on Gleason scores. Four acinar patterns were described, denoted as A, B, C, and D. Our study uncovered a noteworthy presence of RS, predominantly within poorly differentiated tumors. Stromogenic tumors, characterized by high RS content, were particularly associated with Gleason scores of 4 + 3 and ≥ 8. Intriguingly, acinar patterns, including the distinctive B and D patterns, exhibited strong correlations with stromogenic tumors. Incorporating quantitative imaging techniques (Second Harmonic Generation and Two-Photon Excitation Fluorescence Microscopy), we examined collagen fiber density within the stroma. 

Results: our analysis revealed a direct relationship between RS intensity and collagen fiber counts, particularly prominent in patterns B and D. These findings suggest that the stromal reaction in PC is closely linked to acinar morphology and collagen deposition. Moreover, rudimentary microacini at the tumor periphery, associated with intense RS and patterns B and D, may signify an unfavorable prognosis. 

Conclusion: our study highlights the potential of RS as an additional prognostic factor in PC. It underscores the intricate interplay between acinar patterns, RS intensity, and collagen fiber density, providing valuable insights for future prognostic assessments and therapeutic strategies. Further exploration of these relationships is essential for a comprehensive understanding of PC progression and management.

Second Harmonic Generation, collagen, rudimentary microacini
0270-4137
273-282
Junior, Eduardo P.
997ab3d3-15c3-4bc0-89be-9c9c8f003f0a
Gomes, Egleidson F. do Amaral
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de Lima, Mario F.R.
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Raimundo, João V.S.
5b222f2a-d5a0-4d16-a778-1b35f1403c0b
Marinho, Matheus L.
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Soares, Yuri V.C.
ce1127d8-efdf-4df0-b539-73d58ca90d75
Machado, Alexei M.C.
ddfeaa29-294a-4316-aeb2-7e80b607d164
Silva, Gabriel H.C.
f56652eb-b159-4716-b75b-921ee55bb536
Longford, Francis G.J.
27eec433-a773-4cc7-8327-70c5103382e0
Frey, Jeremy
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de Paula, Ana M.
9868f160-10a9-443f-b179-02ca8426003e
Mamede, Marcelo
792632e4-24b7-42d6-934a-d7c5854791ef
Junior, Eduardo P.
997ab3d3-15c3-4bc0-89be-9c9c8f003f0a
Gomes, Egleidson F. do Amaral
968f9638-8d5d-408e-8522-a418ffcf19ef
de Lima, Mario F.R.
7485444e-0f3b-4c38-8121-31c6d842337c
Raimundo, João V.S.
5b222f2a-d5a0-4d16-a778-1b35f1403c0b
Marinho, Matheus L.
8c3d54be-0eca-4050-8f9e-540ba24c4601
Soares, Yuri V.C.
ce1127d8-efdf-4df0-b539-73d58ca90d75
Machado, Alexei M.C.
ddfeaa29-294a-4316-aeb2-7e80b607d164
Silva, Gabriel H.C.
f56652eb-b159-4716-b75b-921ee55bb536
Longford, Francis G.J.
27eec433-a773-4cc7-8327-70c5103382e0
Frey, Jeremy
ba60c559-c4af-44f1-87e6-ce69819bf23f
de Paula, Ana M.
9868f160-10a9-443f-b179-02ca8426003e
Mamede, Marcelo
792632e4-24b7-42d6-934a-d7c5854791ef

Junior, Eduardo P., Gomes, Egleidson F. do Amaral, de Lima, Mario F.R., Raimundo, João V.S., Marinho, Matheus L., Soares, Yuri V.C., Machado, Alexei M.C., Silva, Gabriel H.C., Longford, Francis G.J., Frey, Jeremy, de Paula, Ana M. and Mamede, Marcelo (2025) Reactive stroma and acinar morphology in prostate cancer: implications for progression and prognostic assessment. The Prostate, 85 (3), 273-282. (doi:10.1002/pros.24824).

Record type: Article

Abstract

Introduction: prostate cancer (PC) remains a significant global health concern, with prognostic assessments largely reliant on the Gleason Classification System. While it has proven effective, subjectivity in interpretation persists, prompting the need for complementary approaches. Reactive stroma (RS) has emerged as a potential candidate for enhancing PC characterization, as it reflects intricate interactions among stromal, epithelial, and extracellular matrix components. To shed light on this, we conducted a comprehensive study. 

Methods: two expert pathologists independently analyzed consecutive prostate biopsies (n = 120 patients), categorized into four groups based on Gleason scores. Four acinar patterns were described, denoted as A, B, C, and D. Our study uncovered a noteworthy presence of RS, predominantly within poorly differentiated tumors. Stromogenic tumors, characterized by high RS content, were particularly associated with Gleason scores of 4 + 3 and ≥ 8. Intriguingly, acinar patterns, including the distinctive B and D patterns, exhibited strong correlations with stromogenic tumors. Incorporating quantitative imaging techniques (Second Harmonic Generation and Two-Photon Excitation Fluorescence Microscopy), we examined collagen fiber density within the stroma. 

Results: our analysis revealed a direct relationship between RS intensity and collagen fiber counts, particularly prominent in patterns B and D. These findings suggest that the stromal reaction in PC is closely linked to acinar morphology and collagen deposition. Moreover, rudimentary microacini at the tumor periphery, associated with intense RS and patterns B and D, may signify an unfavorable prognosis. 

Conclusion: our study highlights the potential of RS as an additional prognostic factor in PC. It underscores the intricate interplay between acinar patterns, RS intensity, and collagen fiber density, providing valuable insights for future prognostic assessments and therapeutic strategies. Further exploration of these relationships is essential for a comprehensive understanding of PC progression and management.

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The Prostate - 2024 - Júnior - Reactive Stroma and Acinar Morphology in Prostate Cancer Implications for Progression and - Version of Record
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Accepted/In Press date: 4 November 2024
e-pub ahead of print date: 13 November 2024
Published date: 10 January 2025
Keywords: Second Harmonic Generation, collagen, rudimentary microacini

Identifiers

Local EPrints ID: 508787
URI: http://eprints.soton.ac.uk/id/eprint/508787
ISSN: 0270-4137
PURE UUID: 64896356-c7e4-4c2d-8ccd-a83edf72c731
ORCID for Jeremy Frey: ORCID iD orcid.org/0000-0003-0842-4302

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Date deposited: 03 Feb 2026 17:49
Last modified: 04 Feb 2026 02:32

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Contributors

Author: Eduardo P. Junior
Author: Egleidson F. do Amaral Gomes
Author: Mario F.R. de Lima
Author: João V.S. Raimundo
Author: Matheus L. Marinho
Author: Yuri V.C. Soares
Author: Alexei M.C. Machado
Author: Gabriel H.C. Silva
Author: Francis G.J. Longford
Author: Jeremy Frey ORCID iD
Author: Ana M. de Paula
Author: Marcelo Mamede

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