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KLK3 and TMPRSS2 for molecular lymph-node staging in prostate cancer patients undergoing radical prostatectomy

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KLK3 and TMPRSS2 for molecular lymph-node staging in prostate cancer patients undergoing radical prostatectomy. / Lunger, Lukas; Retz, Margitta; Bandur, Miriam; Souchay, Marc; Vitzthum, Elisabeth; Jäger, Marion; Weirich, Gregor; Schuster, Tibor; Autenrieth, Michael; Kübler, Hubert; Maurer, Tobias; Thalgott, Mark; Herkommer, Kathleen; Koll, Florestan; Gschwend, Jürgen E; Nawroth, Roman; Heck, Matthias M.

In: PROSTATE CANCER P D, Vol. 24, No. 2, 06.2021, p. 362-369.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Lunger, L, Retz, M, Bandur, M, Souchay, M, Vitzthum, E, Jäger, M, Weirich, G, Schuster, T, Autenrieth, M, Kübler, H, Maurer, T, Thalgott, M, Herkommer, K, Koll, F, Gschwend, JE, Nawroth, R & Heck, MM 2021, 'KLK3 and TMPRSS2 for molecular lymph-node staging in prostate cancer patients undergoing radical prostatectomy', PROSTATE CANCER P D, vol. 24, no. 2, pp. 362-369. https://doi.org/10.1038/s41391-020-00283-3

APA

Lunger, L., Retz, M., Bandur, M., Souchay, M., Vitzthum, E., Jäger, M., Weirich, G., Schuster, T., Autenrieth, M., Kübler, H., Maurer, T., Thalgott, M., Herkommer, K., Koll, F., Gschwend, J. E., Nawroth, R., & Heck, M. M. (2021). KLK3 and TMPRSS2 for molecular lymph-node staging in prostate cancer patients undergoing radical prostatectomy. PROSTATE CANCER P D, 24(2), 362-369. https://doi.org/10.1038/s41391-020-00283-3

Vancouver

Lunger L, Retz M, Bandur M, Souchay M, Vitzthum E, Jäger M et al. KLK3 and TMPRSS2 for molecular lymph-node staging in prostate cancer patients undergoing radical prostatectomy. PROSTATE CANCER P D. 2021 Jun;24(2):362-369. https://doi.org/10.1038/s41391-020-00283-3

Bibtex

@article{6ded6ee00342469f8f3266cdb4585900,
title = "KLK3 and TMPRSS2 for molecular lymph-node staging in prostate cancer patients undergoing radical prostatectomy",
abstract = "BACKGROUND: Lymph-node (LN) metastasis in prostate cancer (PC) is a main risk factor for tumor recurrence after radical prostatectomy (RP). Molecular analysis facilitates detection of small-volume LN metastases with higher sensitivity than histopathology. We aimed to prospectively evaluate six candidate gene markers for detection of pelvic LN metastases and to determine their ability to predict biochemical recurrence-free survival (bRFS) in patients treated with RP.METHODS: The expression of kallikrein 2, 3, and 4 (KLK2, KLK3, and KLK4), prostate-specific membrane antigen (PSMA), transmembrane serine protease 2 (TMPRSS2) and transient receptor potential cation channel subfamily M member 8 (TRPM8) was assessed using qPCR. We analyzed LNs from 111 patients (intermediate PC, n = 32 (29%); high-risk PC, n = 79 (71%)) who underwent RP and extended pelvic lymph-node dissection without neoadjuvant treatment.RESULTS: Overall, 2411 LNs were examined by molecular and histopathologic examination. Histopathology detected 69 LN metastases in 28 (25%) patients. KLK2 and KLK3 diagnostically performed best and classified all pN1-patients correctly as molecular node-positive (molN1/pN1). The concordance on LN level was best for KLK3 (96%). KLK2, KLK3, KLK4, PSMA, TMPRSS2, and TRPM8 reclassified 27 (24%), 32 (29%), 29 (26%), 8 (7%), 13 (12%), and 23 (21%) pN0-patients, respectively, as node-positive (pN0/molN1). On multivariable cox regression analysis molecular LN status (molN1 vs. molN0) using KLK3 (HR 4.0, p = 0.04) and TMPRSS2 (HR 5.1, p = 0.02) were independent predictors of bRFS. Median bRFS was shorter in patients with only molecular positive LNs (molN1/pN0) for KLK3 (24 months, p = 0.001) and for TMPRSS2 (12 months, p < 0.001) compared to patients with negative nodes (molN0/pN0) (median bRFS not reached).CONCLUSIONS: For diagnostic purposes, KLK3 showed highest concordance with histopathology for detection of LN metastases in PC patients undergoing RP. For prognostic purposes, KLK3 and TMPRSS2 expression were superior to histopathologic LN status and other transcripts tested for molecular LN status. We suggest a combined KLK3/TMPRSS2 panel as a valuable diagnostic and prognostic tool for molecular LN analysis.",
author = "Lukas Lunger and Margitta Retz and Miriam Bandur and Marc Souchay and Elisabeth Vitzthum and Marion J{\"a}ger and Gregor Weirich and Tibor Schuster and Michael Autenrieth and Hubert K{\"u}bler and Tobias Maurer and Mark Thalgott and Kathleen Herkommer and Florestan Koll and Gschwend, {J{\"u}rgen E} and Roman Nawroth and Heck, {Matthias M}",
year = "2021",
month = jun,
doi = "10.1038/s41391-020-00283-3",
language = "English",
volume = "24",
pages = "362--369",
journal = "PROSTATE CANCER P D",
issn = "1365-7852",
publisher = "NATURE PUBLISHING GROUP",
number = "2",

}

RIS

TY - JOUR

T1 - KLK3 and TMPRSS2 for molecular lymph-node staging in prostate cancer patients undergoing radical prostatectomy

AU - Lunger, Lukas

AU - Retz, Margitta

AU - Bandur, Miriam

AU - Souchay, Marc

AU - Vitzthum, Elisabeth

AU - Jäger, Marion

AU - Weirich, Gregor

AU - Schuster, Tibor

AU - Autenrieth, Michael

AU - Kübler, Hubert

AU - Maurer, Tobias

AU - Thalgott, Mark

AU - Herkommer, Kathleen

AU - Koll, Florestan

AU - Gschwend, Jürgen E

AU - Nawroth, Roman

AU - Heck, Matthias M

PY - 2021/6

Y1 - 2021/6

N2 - BACKGROUND: Lymph-node (LN) metastasis in prostate cancer (PC) is a main risk factor for tumor recurrence after radical prostatectomy (RP). Molecular analysis facilitates detection of small-volume LN metastases with higher sensitivity than histopathology. We aimed to prospectively evaluate six candidate gene markers for detection of pelvic LN metastases and to determine their ability to predict biochemical recurrence-free survival (bRFS) in patients treated with RP.METHODS: The expression of kallikrein 2, 3, and 4 (KLK2, KLK3, and KLK4), prostate-specific membrane antigen (PSMA), transmembrane serine protease 2 (TMPRSS2) and transient receptor potential cation channel subfamily M member 8 (TRPM8) was assessed using qPCR. We analyzed LNs from 111 patients (intermediate PC, n = 32 (29%); high-risk PC, n = 79 (71%)) who underwent RP and extended pelvic lymph-node dissection without neoadjuvant treatment.RESULTS: Overall, 2411 LNs were examined by molecular and histopathologic examination. Histopathology detected 69 LN metastases in 28 (25%) patients. KLK2 and KLK3 diagnostically performed best and classified all pN1-patients correctly as molecular node-positive (molN1/pN1). The concordance on LN level was best for KLK3 (96%). KLK2, KLK3, KLK4, PSMA, TMPRSS2, and TRPM8 reclassified 27 (24%), 32 (29%), 29 (26%), 8 (7%), 13 (12%), and 23 (21%) pN0-patients, respectively, as node-positive (pN0/molN1). On multivariable cox regression analysis molecular LN status (molN1 vs. molN0) using KLK3 (HR 4.0, p = 0.04) and TMPRSS2 (HR 5.1, p = 0.02) were independent predictors of bRFS. Median bRFS was shorter in patients with only molecular positive LNs (molN1/pN0) for KLK3 (24 months, p = 0.001) and for TMPRSS2 (12 months, p < 0.001) compared to patients with negative nodes (molN0/pN0) (median bRFS not reached).CONCLUSIONS: For diagnostic purposes, KLK3 showed highest concordance with histopathology for detection of LN metastases in PC patients undergoing RP. For prognostic purposes, KLK3 and TMPRSS2 expression were superior to histopathologic LN status and other transcripts tested for molecular LN status. We suggest a combined KLK3/TMPRSS2 panel as a valuable diagnostic and prognostic tool for molecular LN analysis.

AB - BACKGROUND: Lymph-node (LN) metastasis in prostate cancer (PC) is a main risk factor for tumor recurrence after radical prostatectomy (RP). Molecular analysis facilitates detection of small-volume LN metastases with higher sensitivity than histopathology. We aimed to prospectively evaluate six candidate gene markers for detection of pelvic LN metastases and to determine their ability to predict biochemical recurrence-free survival (bRFS) in patients treated with RP.METHODS: The expression of kallikrein 2, 3, and 4 (KLK2, KLK3, and KLK4), prostate-specific membrane antigen (PSMA), transmembrane serine protease 2 (TMPRSS2) and transient receptor potential cation channel subfamily M member 8 (TRPM8) was assessed using qPCR. We analyzed LNs from 111 patients (intermediate PC, n = 32 (29%); high-risk PC, n = 79 (71%)) who underwent RP and extended pelvic lymph-node dissection without neoadjuvant treatment.RESULTS: Overall, 2411 LNs were examined by molecular and histopathologic examination. Histopathology detected 69 LN metastases in 28 (25%) patients. KLK2 and KLK3 diagnostically performed best and classified all pN1-patients correctly as molecular node-positive (molN1/pN1). The concordance on LN level was best for KLK3 (96%). KLK2, KLK3, KLK4, PSMA, TMPRSS2, and TRPM8 reclassified 27 (24%), 32 (29%), 29 (26%), 8 (7%), 13 (12%), and 23 (21%) pN0-patients, respectively, as node-positive (pN0/molN1). On multivariable cox regression analysis molecular LN status (molN1 vs. molN0) using KLK3 (HR 4.0, p = 0.04) and TMPRSS2 (HR 5.1, p = 0.02) were independent predictors of bRFS. Median bRFS was shorter in patients with only molecular positive LNs (molN1/pN0) for KLK3 (24 months, p = 0.001) and for TMPRSS2 (12 months, p < 0.001) compared to patients with negative nodes (molN0/pN0) (median bRFS not reached).CONCLUSIONS: For diagnostic purposes, KLK3 showed highest concordance with histopathology for detection of LN metastases in PC patients undergoing RP. For prognostic purposes, KLK3 and TMPRSS2 expression were superior to histopathologic LN status and other transcripts tested for molecular LN status. We suggest a combined KLK3/TMPRSS2 panel as a valuable diagnostic and prognostic tool for molecular LN analysis.

U2 - 10.1038/s41391-020-00283-3

DO - 10.1038/s41391-020-00283-3

M3 - SCORING: Journal article

C2 - 32978525

VL - 24

SP - 362

EP - 369

JO - PROSTATE CANCER P D

JF - PROSTATE CANCER P D

SN - 1365-7852

IS - 2

ER -