Is the Oncotype DX assay necessary in strongly estrogen receptor-positive breast cancers?

The 21-gene Oncotype DX recurrence score (RS) assay quantifies risk of distant recurrence and predicts benefit from chemotherapy in tamoxifen-treated estrogen receptor (ER)-positive, node-negative breast cancer. Although clinically useful, the assay costs roughly $4650. Because the assay is weighted heavily towards expression of ER, our objective was to determine its clinical utility in strongly ER-positive tumors. This was a retrospective study of Huntington Hospital patients undergoing an Oncotype DX assay between 2007 and 2010. Data collected included patient age, expression of ER, progesterone receptor (PR), HER2/neu, ki67, and p53, tumor size, node status, lymphovascular invasion, and nuclear grade. Of 133 total patients, 84 (63.2%) had strongly ER-positive tumors (≥90% expression). Only seven of 84 patients (8.3%) had a high risk RS (>30), indicating statistically significant predicted benefit from chemotherapy. All seven had intermediate to high ki67 expression (>20%) and lower PR expression (≤50%). Our study demonstrates that the clinical utility of the Oncotype DX assay in these patients is limited as most patients with strongly ER-positive tumors will have a low or intermediate RS. Future studies are needed to identify additional predictive factors in these patients with otherwise good prognosis.     

Does oncotype DX recurrence score affect the management of patients with early-stage breast cancer?

BACKGROUND: Oncotype DX is a 21-gene assay that calculates a risk of distant recurrence in women with estrogen-receptor-positive, lymph node-negative breast cancer. The purpose of this study was to determine whether the results of Oncotype DX influence the decision to administer chemotherapy. METHODS: A retrospective study was performed on 85 consecutive patients with estrogen-receptor-positive, lymph node-negative breast cancer who had an Oncotype DX recurrence score (RS) obtained. Tumor size, tumor grade, and treatment were then compared within each risk category. Statistical analysis was performed using STATA software. RESULTS: Tumors that were high grade and Her-2/neu positive more frequently had a high RS. Treatment was changed as a result of Oncotype DX in 44% of patients. CONCLUSIONS: Oncotype DX RS is significantly related to tumor grade and Her2/neu status. In this study, the treatment of 44% of patients was altered as a consequence of Oncotype DX RS.     

An Analysis of Oncotype DX Recurrence Scores and Clinicopathologic Characteristics in Invasive Lobular Breast Cancer

The Oncotype DX breast cancer assay (Genomic Health, Redwood City, CA) is increasingly being used to guide treatment decisions for patients with early stage, hormone‐positive, Her‐2‐negative breast cancer. The utility of the Oncotype DX in decision making for treatment of invasive lobular carcinoma (ILC) has not been investigated as the results reported by Genomic Health are largely in a population with invasive ductal carcinoma (IDC). The authors hypothesized that the Oncotype DX recurrence score (RS) distribution for ILC is different than that for IDC. We performed a retrospective analysis of early stage breast cancer patients treated at Penn State Cancer Institute from 2001 to 2011 and identified 102 patients with ILC. We also pulled RS data from our institution's prospective registry of consecutive patients with early stage IDC treated during the same time period. Median follow‐up was 55 months. We found that the RS distribution for ILC differed significantly from that of IDC (p = 0.024). We also found a statistically significant difference in the RS distribution between the pure ILC and pleomorphic ILC subtypes (p = 0.027). The Oncotype DX RS distribution in ILC is unique, differing significantly from that in ductal carcinoma. Consequently, the clinical usefulness and cost‐effectiveness of the Oncotype DX in guiding treatment for ILC should be further investigated.     

Selection of neoadjuvant treatment based on the 21-GENE test results in luminal breast cancer

Neoadjuvant chemotherapy (NAC) is an optimal option in early breast cancer, but in ER-positive/HER2-negative (luminal) is still controversial, although a survival benefit has recently been observed when a histological response by Symmans’ method type 0 or I is achieved. The 21-gene Oncotype DX Breast Recurrence Score® assay (Oncotype DX®) is a validated test to assess the survival benefit of adjuvant chemotherapy in these patients but its role in the neoadjuvant setting is less established. We analyzed the results of the Oncotype DX® test in a cohort of 122 consecutive patients selected to receive NAC based on classical clinicopathological parameters and the correlation between the Oncotype DX® results and the pathological response assessed by Symmans’ method. Median age was 56.5 (range 31–84) years. Initial tumor size was T1 (<20 mm) in 46 patients (37.7%), 57 (46.7%) had a T2 tumor (20–50 mm), and 19 (15.6%) had a tumor size more than 50 mm. 59 (48.4%) had axillary node involvement. The median expression estrogen and progesteron receptors by immunohistochemistry was 280 and 120 respectively and median Ki67 index was 28%. The Recurrence Score (RS) results were <11 in 21 patients (17.2%) patients, RS 11 to 25 in 58 (47.5%), and RS > 25 in 43 (35.2%). Considering the Oncotype DX test results, neoadjuvant chemotherapy was administered to 60 patients (49%), 11 (9%) received adjuvant chemotherapy and 51 (42%) no chemotherapy. Testing with the assay has therefore led to 42% fewer chemotherapy treatments. Among 60 patients receiving NAC, pathologic response was achieved for 5 patients (8.3%) with RCB-0 and 15 RCB-1 (25%). We did not find any pathological response RCB-0 and RCB-I in the 20 patients who received NAC and had a Recurrence Score result <21 for the premenopausal group, or a RS result <25 for the postmenopausal group. For patients with highest Recurrence Score results (RS > 21 or 25 according to menopausal status) it was 12% (5/40) RCB-0 and 40% (16/40) RCB-I.ConclusionsThe Oncotype DX test could be a useful tool to select patients candidates for neoadjuvant chemotherapy in luminal breast cancer. Neoadjuvant chemotherapy could be avoided in 42% of patients. We found a correlation between Recurrence Score results and pathological response with 14% of RCB-0 and a total of 47% of significant pathological response type RCB-0 and RCB-I in patients with highest Recurrence Score results. Interestingly, patients with a Recurrence Score result inferior to 32 did not get any histological response type 0 and only 5% RCB-I.     

Impact of Oncotype DX on Treatment Decisions in ER‐Positive,Node‐Negative Breast Cancer with Histologic Correlation

Oncotype DX, a gene‐expression profiling assay, provides stratification of patients with estrogen‐receptor positive, lymph‐node‐negative early breast cancer into risk groups based on recurrence score, which are associated with distant recurrence and response to chemotherapy. This study aims to determine whether Oncotype DX influences clinicians' treatment decisions, and whether assay results correlate with histologic assessment. Fifty patients with estrogen‐receptor positive, node‐negative early breast cancer analyzed by Oncotype DX and operated on by two breast surgeons were included. To assess effect on treatment decisions, clinical vignettes were created by retrospective chart review. Physicians were then presented with the clinical vignettes and instructed to make a treatment decisions (i.e., hormone therapy alone versus hormone therapy combined with chemotherapy) both before and after knowledge of the recurrence score. To assess correlation with histologic assessment, a prospective, blinded review of tumor slides was performed by two pathologists. Based on this review, tumors were placed into low, intermediate and high risk groups for comparison with Oncotype DX assay results. Treatment decisions were changed based on Oncotype DX results in 36 and 18% of cases by breast surgeons and medical oncologists, respectively. All tumors categorized as high risk by Oncotype DX were categorized as high risk based on histologic assessment, and 96% of cases categorized as low risk by recurrence score were categorized as low or intermediate risk by histologic assessment. Oncotype DX significantly influences management of estrogen‐receptor positive, lymph‐node‐negative early breast cancer. Further studies are needed to assess association of histologic categorization to assay results.     

Breast Cancers of Special Histologic Subtypes Are Biologically Diverse

Background/Objective

Cancers classified as “special histologic subtypes” are felt to have a good prognosis. We used the 21-gene Oncotype DX Breast Recurrence Score^® multigene assay to examine prognostic variation within special histologic subtypes. We also examined the Recurrence Score^® (RS) distribution among the more common ductal (IDC) and lobular (ILC) cancers.

Methods

610,350 tumor specimens examined in the Genomic Health clinical laboratory from 2/2004 to 8/2017 were included. Specimen histology was classified centrally using a single H&E slide and World Health Organization criteria. RS distribution (low?<?18, intermediate 18–30, and high?≥?31) was compared among histologic subtypes.

Results

Median patient age was 60 years (IQR 51–67); 80% were node negative. Most patients had low RS results (59.2%); only 9.5% had high results. The lowest mean RS was seen in the papillary subtype (11); the highest in the IDC group (18.4). Mean RS for all special subtypes was lower than that of IDC patients. When the high RS threshold was decreased from 31 to 25, as used in the TAILORx and RxPONDER trials, the number of high RS-result patients increased from 9.5% to 16.8%. Patients with ILC had a lower mean RS result than patients with IDC, 16.5 versus 18.4.

Conclusion

There is substantial diversity in predicted prognosis among patients with cancers classified as special histologic subtypes, with 12–25% having intermediate RS results and 0.5–9% having high RS results. Pending further definition of the role of chemotherapy for patients with intermediate RS results by TAILORx and RxPONDER, the RS result may help to inform systemic therapy decisions in these patients.

     

ER and PR Immunohistochemistry and HER2 FISH versus Oncotype DX: Implications for Breast Cancer Treatment

Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor (HER2) concordance between immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), and Oncotype DX, a commercially available RT‐PCR‐based assay which recently began reporting biomarker results was assessed. ER concordance was 98.9% (262/265), Pearson correlation coefficient (r) = 0.42, and Spearman's rank correlation (ρ) = 0.25. Positive percent agreement for ER was 98.9% (262/265). One patient with discordant ER results was not offered hormone therapy based on the preferential use of Oncotype DX. PR was concordant in 91.3% (242/265), r = 0.80, ρ = 0.75, and Cohen's kappa (κ) = 0.63. Positive percent agreement for PR was 90.5% (218/241) and negative percent agreement was 100% (24/24). HER2 concordance was 99.2% (245/247), r = 0.35, ρ = 0.28, and κ = 0.12. Positive percent agreement for HER2 was 0% (0/2) and negative percent agreement was 100% (245/245). Of the three FISH HER2‐amplified cases, two were negative and one was equivocal, and all FISH HER2‐equivocal cases (n = 3) were negative by Oncotype DX. Patients that were FISH HER2‐amplified, Oncotype DX HER2‐negative did not receive trastuzumab. Although our results demonstrated high concordance between IHC and Oncotype DX for ER and PR, our data showed poor positive percent agreement for HER2. Compared to FISH, Oncotype DX does not identify HER2‐positive breast carcinomas. The preferential use of Oncotype DX biomarker results over IHC and FISH is discouraged.     

HER2 equivocal breast cancer that is positive by alternative probe HER2 FISH are classified as HER2 negative by Oncotype DX

In breast cancer, human epidermal growth factor receptor 2 (HER2) status is determined by immunohistochemistry (IHC) and/or in situ hybridization. Oncotype DX also reports HER2 status by an rt‐PCR‐based assay. Assay concordance between IHC and fluorescent in situ hybridization (FISH) (including alternative probe HER2 FISH) vs Oncotype DX HER2 rt‐PCR has not been described in the post‐2013 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) HER2 Guideline revision setting. We performed a retrospective review of HER2 equivocal invasive breast carcinoma from 2014 to 2016 with the Oncotype DX HER2 result. Fifteen patients with HER2 equivocal invasive breast cancer had Oncotype DX performed. Of these, 13 underwent alternative probe HER2 FISH yielding 4 negative, 6 equivocal and 3 positive results. All 15 cases were classified as HER2 negative by Oncotype DX rt‐PCR, including the three cases which were positive by alternative probe HER2 FISH, yielding a discordance rate for Oncotype DX rt‐PCR HER2 of 20% (3/15). All three patients with HER2‐positive breast cancer on the basis of alternative probe HER2 FISH received anti‐HER2‐targeted therapy. Treatment decisions based on HER2 status should utilize the IHC/FISH result as Oncotype DX results may incorrectly disqualify some patients from being eligible for anti‐HER2 therapy based on the current 2013 ASCO/CAP HER2 Guidelines.     

Is Oncotype DX Recurrence Score (RS) of Prognostic Value Once HER2‐Positive and. Low‐ER Expression Patients are Removed?

Oncotype DX has been criticized for not providing significantly more prognostic information than histopathologic analysis. Oncotype DX was validated in cohorts that included poor prognostic factors (HER2‐positive, low‐estrogen receptor [ER] expression), raising the question: if patients with known high recurrence rates are excluded, is the Recurrence Score (RS) still valid? Our purpose was to determine if RS can be predicted with readily available measures. One hundred and twenty samples from August 2006 to November 2010 that underwent Oncotype DX testing were analyzed. Data included RS, ER, progesterone receptor (PR), HER2, and Ki67 status by immunohistochemistry (IHC). IHC data were used to create two linear regression models to predict RS. SAS's JMP‐7 was used for statistical analysis. When comparing Oncotype DX‐ and IHC‐derived ER and PR values, there were 21 discordant samples. The linear regression model PRS‐F created with IHC data (ER, PR, HER2, Ki67) from all samples (n = 120) had an adjusted R² = 0.60 indicating a good model for predicting RS. The PRS‐R model was built without low‐ER and HER2‐positive samples (n = 110). It had an adjusted R² = 0.38 indicating poor prediction of RS. Oncotype DX data showed good concordance with IHC for ER‐ and PR‐expression in this cohort. Low‐ER samples had high RS. After removing low‐ER and HER2‐positives, calculating RS with PRS‐R from remaining data showed poor predictive power for RS (adjusted R² = 0.38). This result questions whether RS is prognostic in this subgroup (who would most benefit from further clarification of recurrence risk) and independent of pathology, or is simply producing random RS values. Data bases available to Genomic Health can resolve this issue.     

Changing paradigms in breast cancer management: introducing molecular genetics into the treatment algorithm

Advances in molecular genetics aimed at individualizing breast cancer treatment have been validated. We examined the use of gene assays predictive of distant recurrence in breast cancer and their impact on adjuvant treatment. A retrospective chart review of 58 T1/T2, node-negative, estrogen-receptor positive breast cancer patients that underwent Oncotype DX gene assay testing between January and December 2006 was performed. We compared treatment received after gene assay evaluation to treatment based on National Comprehensive Cancer Network guidelines. Patients were grouped using these recommendations: Low-risk group (T1a/T1b), no chemotherapy; High-risk group (T1c/T2), chemotherapy. Oncotype DX recommendations are as follows: Low recurrence risk, no chemotherapy; high recurrence risk, chemotherapy. A change in management was defined as chemotherapy for T1a/T1b disease and no chemotherapy for T1c/T2 disease. Two T1a/T1b patients had high risk of recurrence per gene assay scores and were treated with chemotherapy (P < 0.05). Eighteen T1c/T2 patients had low recurrence risk scores; 13 (72%) were spared chemotherapy. The recurrence score increased the number of patients classified as low risk of recurrence by 12 per cent and downstaged 63 per cent of high-risk patients (P < 0.003). Gene assay results changed management in 15 of 58 (26%) patients (P < 0.05). The use of gene assays allowed us to better tailor treatment in a significant number of our patients.     

Is There a Role for Oncotype Dx Testing in Invasive Lobular Carcinoma?

Oncotype Dx Breast Cancer Assay is a 21‐gene assay used in estrogen receptor (ER)‐positive breast cancer to predict benefit from chemotherapy (CT). Tumors are placed into one of three risk categories based on their recurrence score (RS). This paper explores the impact of tumor histopathologic features and Oncotype Dx RS on the treatment plan for invasive lobular carcinoma (ILC). Invasive lobular carcinoma cases submitted for Oncotype Dx testing were identified from a clinical data base. The histopathologic and immunohistochemical features and RS subcategory of each tumor, and treatment regimen and medical oncologic assessments of each patient were reviewed. A total of 135 cases of ILC had RS testing, which represented 15% of all ILC diagnosed at the institution over the time period. 80% of ILC was of the classical subtype and all tumors were ER positive and human epidermal growth factor receptor 2 (HER‐2) negative by immunohistochemistry. Sixty three percent of cases were low risk (LR), 35.5% were intermediate risk (IR) and 1.5% were high risk (HR). Both HR cases were pleomorphic ILC. Sixty eight percent of classical ILC had a LR score, while 70% of pleomorphic ILC had an IR score. Patients in the IR category were significantly more likely to undergo CT than patients in the LR category (54% versus 18%; p < 0.0001). In the LR category, those undergoing CT were significantly younger and more likely to have positive lymph nodes (p < 0.05). Qualitative analysis of medical oncologic assessments showed that RS played a role in decision‐making on CT in 74% of cases overall. At our institution, Oncotype Dx RS currently plays a role in the management of a proportion of ILC and impacts on treatment decisions.     

The biology of male breast cancer

Important differences have begun to emerge concerning the molecular profile of female and male breast cancer which may prove to be of therapeutic value. This review examined all the available data on the genomics of MBC. Most male cancers are ER+ve but without a corresponding increase in PR positivity and only a weaker association with estrogen-controlled markers such as PS2, HSP27 and Cathepsin-D. HER2 +ve cancers are rare in males and the role of androgen receptor is controversial. Although the Luminal A phenotype was the most frequent in both MBC and FBC, no Luminal B or HER2 phenotypes were found in males and the basal phenotype was very rare. Using hierarchical clustering in FBC, ERα clustered with PR, whereas in MBC, ERα associated with ERβ and AR. Based on limited data it appears that Oncotype DX is effective in determining recurrence risk in selected MBC. In future, tailored therapies based on genomics will probably yield the most promising approach for both MBC and FBC.     

The Relationship of Race,Oncotype DX,and Ki67 in a Population Highly Screened For Breast Cancer

Oncotype DX recurrence score (ODX) can predict risk of invasive breast cancer recurrence and benefit of chemotherapy. Literature is limited on the relationship of ODX and race in women with hormone receptor positive and node negative/positive disease. Our study examines the relationship between race and clinical characteristics within a population of highly screened women with newly diagnosed breast cancer. The institutional Breast Cancer Database was queried for patients with newly diagnosed breast cancer between January2010 and March2015. We analyzed clinical and tumor characteristics including ODX. Statistical analyses included Pearson's Chi‐Square and Fisher's Exact Tests. There were 2,092 women in our study cohort. The majority had college‐level education (84%), regular screening (78%), and clinical breast exams (88%). The majority had invasive ductal carcinoma (IDC) (62%), early stage (0, I, II) tumors (93%), ER+ (84%), PR+ (71%), Her2 negative (86%), and node negative disease (83%). There was a significantly higher proportion of later stage disease among African‐Americans (p = 0.001) and Asians (p = 0.006) and more triple negative breast cancers among African‐Americans (p < 0.0001). A majority of patients had a low ODX (56%). While ODX was not different among the race categories (p = 0.97), there were significant racial differences in Ki‐67 (p < 0.0001). In a population of highly screened women, differences were found between races regarding tumor histology. No statistical difference between race and ODX was noted, but there were racial differences in Ki67. Therefore we recommend that further research be focused on refining management algorithms by ethnicity.     

乳腺癌多基因检测及其临床意义

多基因检测对于乳腺癌的预后判断和治疗方案选择具有重要的参考意义,特别是对雌激素受体阳性病人。近年来一些多基因诊断模型被美国临床肿瘤学会（ASCO）、圣加伦标准、美国国家综合癌症网络（NCCN）等多个权威乳腺癌诊疗指南所采用,并开展了临床应用。IHC4评分、MammaPrint、PAM50、Oncotype DX、Genomic grade index、Breast Cancer Index、EndoPredict和同源重组缺陷评分为7个代表性的乳腺癌多基因检测方法,不但可以用于转移复发生存风险的预测,还可以对治疗有指导意义。     

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??Multi-gene testing in breast cancer and clinical significance MA Rong*, WANG Jian-li. *Department of Breast Surgery, Qilu Hospital of Shandong University, Jinan 250012, China
Corresponding author: MA Rong, E-mail: marongw2000@163.com
Abstract Multi-gene testing (MGT) can provide information that could assist prognosis prediction and therapeutic decision-making in ER-positive cancers. Recently, many MGT models have been endorsed by the American Society of Clinical Oncology, St.Gallen and National Comprehensive Cancer Network guidelines. A panel of clinically validated MGT models including IHC4 score, MammaPrint, PAM50, Oncotype DX, Genomic grade index, Breast Cancer Index, EndoPredict and homologous recombination deficiency score are seven typical MGT, which can predict the risk of metastasis and recurrence and guide the therapy of breast cancer.     

Impact of biomarkers and genetic profiling on breast cancer prognostication: A comparative analysis of the 8th edition of breast cancer staging system

The 8th edition of the American Joint Committee on Cancer (AJCC) staging guidelines combine traditional TNM system with biomarkers to reflect our current understanding of tumor biology and targeted therapy. In this study, we investigated the impact of the TNM + Biomarkers staging system and the additive value of Oncotype Dx? genomic profile recurrence score (RS) (TNM + Biomarkers+RS <11) for the staging of breast cancer (BC) using data from two tertiary referral cancer centers. Compared to TNM alone, the TNM + Biomarkers system changed the stage group in 32.7% of BCs (27% downstage, 5.7% upstage). Most (98.3%) of the downstaged BCs were estrogen receptor (ER)+/progesterone receptor (PR)+, whereas 78% of the upstaged BCs were ER?/PR?/human epidermal growth factor receptor 2 (HER2)?. Compared to TNM + Biomarkers staging, the addition of genetic profile data (TNM + Biomarker+RS <11) downstaged only <1% BCs. Our analysis suggests that for T1‐T2N0 ER+/HER2? BCs, Oncotype Dx? RS <11 provides added value as a staging parameter only in a very small group of cases compared to TNM + Biomarkers alone.     

Should women with early breast cancer under 40 years of age have a routine 21-gene recurrence score testing: A SEER database study

PurposeTo investigate the effect of 21-gene recurrence score (RS) on chemotherapy-decision making and prognosis in breast cancer patients aged <40 years.MethodsUsing the Surveillance, Epidemiology, and End Results program, we included patients aged <40 years with tumor size ≤5 cm, node negative, and estrogen receptor-positive breast cancer between 2004 and 2015. Correlations among the 21-gene RS, chemotherapy decision-making and prognosis were analyzed.ResultsWe included 2721 patients in this study. According to TAILORx cutoffs, 352 (12.9%), 1814 (66.7%), and 555 (20.4%) patients were classified as low-, intermediate-, and high-risk cohorts, respectively. The 21-gene RS categories were associated with the probability of receiving chemotherapy, with 7.1%, 33.4%, and 77.1% of patients in low-, intermediate-, and high-risk cohorts treated with chemotherapy, respectively (P < 0.001). Those in the intermediate-risk cohort were significantly less likely to receive chemotherapy over time (P = 0.008), and the trends of chemotherapy receipt were stable in the low-risk and high-risk cohorts over time. Multivariate analysis showed that the 21-gene RS was an independent prognostic indicator for breast cancer specific survival. In the stratified analysis, the receipt of chemotherapy was associated with better breast cancer specific survival in the high-risk cohort (P = 0.028), but not in the intermediate-risk cohort (P = 0.223).Conclusions21-gene RS has clinical implications for young breast cancer patients with respect to optimizing chemotherapy-decisions. Despite increasing rates of chemotherapy receipt in young patients, more studies are needed to determine the definitive effect of chemotherapy in young patients with three RS categories.     

Cyclin E and Ki67 (MIB1) as markers of proliferative activity in human prostate cancers: an immunohistochemical study

Recent evidence has implicated cyclins in the evolution and progression of various malignancies. We immunohistochemically evaluated the expression of cyclin E, a G1 cyclin, along with Ki67-assessed proliferative activity in prostatic carcinoma. Formalin-fixed, paraffin embedded tissue sections from eighty-four previously untreated prostate carcinomas were distributed according to tumor grade and examined for the expression of cyclin E. Results were compared with Ki67 expression as well as tumor grade. Cyclin E was detected in 22 of 84 cases (26.2%) and its expression varied substantially (mean index varied from 4,7–9,0). Ki67 staining was present in 35.7% of cases. Although no correlation with tumor grade was found for either cyclin E or Ki67, a statistically significant correlation was present between the expression of the two biomarkers (Fisher's test, p<0.0001). We examined the proliferative activity of prostatic carcinomas of different tumor grades with markers for Ki67 and cyclin E. Our findings indicate that reactivities with these markers are strongly correlated with each other but their expression seems independent of tumor grade. Further studies on the clinical implications of the combined variable of cyclin E and Ki67 expression might disclose a useful prognostic indicator of survival or tumor relapse in patients with prostate carcinoma.     

Expression of p27<Superscript>(Kip1)</Superscript>, cyclin D3 and Ki67 in BPH,prostate cancer and hormone-treated prostate cancer cells

p27^(Kip1), cyclin D3 and Ki67 are the markers of DNA damage and cell proliferation. The goal of the current study was to analyze expression of the markers in benign and malignant prostate cancer tissues. Activity of p27^(Kip1), cyclin D3 and Ki67 was immunohistochemically evaluated in different cells of BPH, prostate cancer (PCa) and hormonally treated prostate cancer (HTPCa) tissues. The tissue samples were derived by means of TURP or radical prostatectomy. Intensity of the expression was compared between the groups, and association was sought with clinical parameters. Total expression of p27^(Kip1) was significantly higher in BPH as compared with PCa. Epithelial marker expression was higher in HTPCa than in PCa. Intensity of the expression in epithelial, vascular and ductal cells was negatively associated with the tumor stage and Gleason grades. Total Ki67 activity was positively correlated with patient age and serum PSA level. There was significantly higher expression in PCa and hormone-escaped PCa (HEPCa) as compared with BPH. Epithelial and vascular marker expression was positively associated with tumor stage and Gleason grades. There was a positive correlation between cyclin D3 and serum PSA level. With the increase of Gleason grades, cyclin D3 expression increased significantly. Expression of p27^(Kip1) negatively correlated with Ki67 and cyclin D3, while the latter two markers correlated positively. p27^(Kip1) is down-regulated, whereas Ki67 and cyclin D3 are up-regulated in PCa. Intensity of the markers’ expression is associated with tumor stage and grades. Hormonotherapy of PCa causes activation of p27^(Kip1). HEPCa is characterized by increased Ki67 expression.