Increasing Immune Dysfunction is Associated with Increasing Matrix-Metalloproteinase-2 Expression and Predicts Biochemical Failure in Men with Bone Marrow Micro-Metastasis Positive Localized Prostate Cancer
INTRODUCTION: To determine if there was an association of the ALC (absolute lymphocyte count) and LCP (lymphocytopenia) with the expression of MMP-2 in bone marrow micro-metastasis, the changes occurring during follow-up and association with biochemical failure.
METHODS AND PATIENTS: One month after surgery blood and bone marrow samples were taken to determine the presence of micro-metastasis, the presence of circulating prostate cells (CPCs) and ALC. CPCs and micro-metastasis were detected using immunocytochemistry and MMP-2 expression determined in micro-metastasis. Only men positive for micro-metastasis participated in the study. At end follow blood was taken for serum PSA, ALC and CPCs, if the ALC decreased by more than 10% bone marrow sampling was repeated and MMP-2 expression determined, similarly for men with BF. Men who had stable ALCs had an end of study evaluation of the bone marrow.
RESULTS: 402 men underwent radical prostatectomy, one month post surgery 79 men were positive for only bone marrow micro-metastasis and formed the study group; of whom 36/79 (45%) underwent BF. Clinical pathological findings were not significantly different between men with or without BF. In men with BF the ALC was significantly lower one-month post surgery. The 5 and 10 year Kaplan-Meier survival was 100% at 5-years and 65% at 10-years for the whole cohort. Men without BF had stable ALCs. A decrease of >10% in the ALC was associated with increasing MMP-2 expression in the micro-metastasis and surrounding stromal tissue, the appearance of CPCs 6-12 months later and BF.
CONCLUSIONS: the immune host-tumour cell interaction in the microenvironment is dynamic and changes with time. A decreasing ALC may be a valuable marker in identifying men with high risk of BF and changes in immune mediated dormancy before the PSA rises.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:23 |
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| Enthalten in: |
Asian Pacific journal of cancer prevention : APJCP - 23(2022), 7 vom: 01. Juli, Seite 2497-2505 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Murray, Nigel P [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 01.08.2022 Date Revised 10.12.2022 published: Electronic Citation Status MEDLINE |
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| doi: |
10.31557/APJCP.2022.23.7.2497 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM344210863 |
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| 100 | 1 | |a Murray, Nigel P |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Increasing Immune Dysfunction is Associated with Increasing Matrix-Metalloproteinase-2 Expression and Predicts Biochemical Failure in Men with Bone Marrow Micro-Metastasis Positive Localized Prostate Cancer |
| 264 | 1 | |c 2022 | |
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| 500 | |a Date Completed 01.08.2022 | ||
| 500 | |a Date Revised 10.12.2022 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a INTRODUCTION: To determine if there was an association of the ALC (absolute lymphocyte count) and LCP (lymphocytopenia) with the expression of MMP-2 in bone marrow micro-metastasis, the changes occurring during follow-up and association with biochemical failure | ||
| 520 | |a METHODS AND PATIENTS: One month after surgery blood and bone marrow samples were taken to determine the presence of micro-metastasis, the presence of circulating prostate cells (CPCs) and ALC. CPCs and micro-metastasis were detected using immunocytochemistry and MMP-2 expression determined in micro-metastasis. Only men positive for micro-metastasis participated in the study. At end follow blood was taken for serum PSA, ALC and CPCs, if the ALC decreased by more than 10% bone marrow sampling was repeated and MMP-2 expression determined, similarly for men with BF. Men who had stable ALCs had an end of study evaluation of the bone marrow | ||
| 520 | |a RESULTS: 402 men underwent radical prostatectomy, one month post surgery 79 men were positive for only bone marrow micro-metastasis and formed the study group; of whom 36/79 (45%) underwent BF. Clinical pathological findings were not significantly different between men with or without BF. In men with BF the ALC was significantly lower one-month post surgery. The 5 and 10 year Kaplan-Meier survival was 100% at 5-years and 65% at 10-years for the whole cohort. Men without BF had stable ALCs. A decrease of >10% in the ALC was associated with increasing MMP-2 expression in the micro-metastasis and surrounding stromal tissue, the appearance of CPCs 6-12 months later and BF | ||
| 520 | |a CONCLUSIONS: the immune host-tumour cell interaction in the microenvironment is dynamic and changes with time. A decreasing ALC may be a valuable marker in identifying men with high risk of BF and changes in immune mediated dormancy before the PSA rises | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Immune function | |
| 650 | 4 | |a Prostate Cancer | |
| 650 | 4 | |a biochemical failure | |
| 650 | 4 | |a lymphocytopenia | |
| 650 | 4 | |a minimal residual disease | |
| 650 | 7 | |a Prostate-Specific Antigen |2 NLM | |
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| 650 | 7 | |a MMP2 protein, human |2 NLM | |
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| 650 | 7 | |a Matrix Metalloproteinase 2 |2 NLM | |
| 650 | 7 | |a EC 3.4.24.24 |2 NLM | |
| 700 | 1 | |a Aedo, Socrates |e verfasserin |4 aut | |
| 700 | 1 | |a Fuentealba, Cynthia |e verfasserin |4 aut | |
| 700 | 1 | |a Reyes, Eduardo |e verfasserin |4 aut | |
| 700 | 1 | |a Salazar, Anibal |e verfasserin |4 aut | |
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