Cell Proliferation Assessed by Ki-67 Immunoreactivity on Formalin Fixed Tissues is a Predictive Factor for Survival in Prostate Cancer

Stattin, Pär; Damber, Jan‐Erik; Karlberg, Lars; Bergh, Anders

doi:10.1097/00005392-199701000-00067

Cited by 28 publications

(42 citation statements)

References 14 publications

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“…14,17,18,21 In addition, two studies have examined the prognostic utility of Ki-67 LI in prostate cancer patients managed conservatively. 20,22 Both demonstrated a significant association between Ki-67 LI and prostate cancer disease-free survival. However, these studies included patients with high-risk disease, assessed Ki-67 LI on TURP tissue, and did not include analysis of baseline PSA levels.…”

Section: Discussionmentioning

confidence: 96%

“…14,18 The prognostic role of Ki-67 LI has also been established for prostate cancer-specific survival in patients managed by watchful waiting. 19,20 Importantly however, none of these studies were targeted at men with low-risk localized disease who are suitable for management by active surveillance. In addition, the techniques used to evaluate Ki-67 LI in all of these studies were not suitable for analysis of multiple markers in a high-throughput fashion.…”

Section: Introductionmentioning

confidence: 99%

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Biopsy tissue microarray study of Ki-67 expression in untreated, localized prostate cancer managed by active surveillance

Jhavar

Bartlett

Kovács

et al. 2008

Prostate Cancer Prostatic Dis

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Active surveillance provides a unique opportunity to study biomarkers of prostate cancer behaviour, although only small volumes of tumor tissue are typically available. We have evaluated a technique for constructing tissue microarrays (TMAs) from needle biopsies for assessing immunohistochemical markers in localized prostate cancer managed by active surveillance. TMAs were constructed from diagnostic prostate biopsies for 60 patients with localized prostatic adenocarcinoma in a prospective cohort study of active surveillance. Radical treatment was recommended for a prostate-specific antigen (PSA) velocity greater than 1 ng ml À1 per year or adverse histology in repeat biopsies, defined as Gleason score X4 þ 3 or 450% of cores involved. Sections from the TMAs were stained with H&E, P63/AMACR and Ki-67. Time to radical treatment was analysed with respect to clinical characteristics and Ki-67 LI. At a median follow up of 36 months, 25/60 (42%) patients had received radical treatment. On univariate analysis, PSA density (P ¼ 0.001), Gleason score (P ¼ 0.001), clinical T stage (P ¼ 0.01), Ki-67 LI (P ¼ 0.02) and initial PSA (P ¼ 0.04) were associated with time to radical treatment. On multivariate analysis, PSA density (P ¼ 0.01), Ki-67 LI (P ¼ 0.03) and Gleason score (P ¼ 0.04) were independent determinants of progression to radical treatment. TMAs constructed from prostate needle biopsies can be used to assess immunohistochemical markers in localized prostate cancer managed by active surveillance. Ki-67 LI merits further study as a possible biomarker of early prostate cancer behaviour.

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Biopsy tissue microarray study of Ki-67 expression in untreated, localized prostate cancer managed by active surveillance

Jhavar

Bartlett

Kovács

et al. 2008

Prostate Cancer Prostatic Dis

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“…Prostate cancer-specific and relative survival was very similar, indicating a correct evaluation of the cause of death. 33 The Research Ethics committee in Umeå, Sweden, approved the study.…”

Section: Patientsmentioning

confidence: 99%

Prostate Cancer Increases Hyaluronan in Surrounding Nonmalignant Stroma, and This Response Is Associated with Tumor Growth and an Unfavorable Outcome

Josefsson

Adamo

Hammarsten

et al. 2011

The American Journal of Pathology

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Our objective was to investigate whether the presence of a tumor increases hyaluronan (HA) levels in surrounding prostate tissues and whether this extratumoral HA influences tumor growth and outcome. From a series of 287 men diagnosed with prostate cancer at transurethral resection and followed up with watchful waiting, tissue microarrays were constructed, stained, and scored for HA. A high HA staining score in the tumor stroma or in nonmalignant prostate tissue stroma were both associated positively with higher Gleason score and larger tumor volume, and was associated with a poor outcome. HA staining score was not an independent marker for outcome (multivariate Cox, with Gleason score, tumor volume, stage, and HA variables). In an orthotopic rat prostate cancer model, hyaluronic acid synthase-1 mRNA levels and HA staining were increased in normal prostate tissue surrounding prostate cancer. Orthotopic prostate cancer growth was increased by intraprostatic injection of HA. In conclusion, cancer in the prostate apparently stimulates HA synthesis both in tumor stroma and in the surrounding normal tissue. This promoted tumor growth and was associated with an unfavorable outcome. (Am J Pathol

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“…Numerous reports exist on the utility of tumour proliferative activity in solid cancers for predicting prognosis (Statin et al, 1997) and most studies show Ki-67 to have greater predictive value than proliferating cell nuclear antigen (Leonardi et al, 1992).…”

Section: Discussionmentioning

confidence: 99%

Prediction of relapse after lymph node dissection for germ cell tumours: can salvage chemotherapy be avoided?

et al. 2001

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Salvage chemotherapy has been used by some oncology centres for patients with residual malignant or immature elements in retroperitoneal lymph node dissections removed for metastatic non-seminomatous germ cell tumours. However, surveillance of these patients shows that many are cured by surgery alone. 118 retroperitoneal lymph node dissections for metastatic non-seminomatous germ cell tumours were reviewed and the morphology seen within them was quantified. 28 of these had immature or malignant elements and had been treated by surveillance before administration of further chemotherapy. The proliferation rate in these cases was assessed by immunochemistry. The proliferation index and the amount of embryonal carcinoma (EC) were both predictors of recurrence and therefore the need for further chemotherapy. Patients with greater than 25% of EC had an 84% chance of relapse and those with a Ki-67 index of greater than 50% had a 71% chance of relapse. The two tests had a positive predictive value of 83% and 71%, respectively. Patients with such a high risk of recurrence could be considered for post-operative adjuvant therapy at this point whilst others would be suitable for a watchful waiting approach. © 2001 Cancer Research Campaign http://www.bjcancer.com

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Cell Proliferation Assessed by Ki-67 Immunoreactivity on Formalin Fixed Tissues is a Predictive Factor for Survival in Prostate Cancer

Abstract: Our study indicates that proliferation rate, assessed by Ki-67 immunoreactivity in formalin fixed tissues, is a predictive marker for outcome in prostate cancer.

Cited by 28 publications

References 14 publications

Biopsy tissue microarray study of Ki-67 expression in untreated, localized prostate cancer managed by active surveillance

Biopsy tissue microarray study of Ki-67 expression in untreated, localized prostate cancer managed by active surveillance

Prostate Cancer Increases Hyaluronan in Surrounding Nonmalignant Stroma, and This Response Is Associated with Tumor Growth and an Unfavorable Outcome

Prediction of relapse after lymph node dissection for germ cell tumours: can salvage chemotherapy be avoided?

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