Topoisomerase 1A, HER/2neu and Ki67 expression in paired primary and relapse ovarian cancer tissue samples

In the present study we examined prognostic value of immunohistochemical estimation of topoisomerase 1A (TOP 1A) and HER-2/neu expression in ovarian cancers treated with platinum-based drugs but not with topotecan and the relation between expression of these proteins on the one hand and intensity of proliferation (Ki67) on the other. The analyses were performed on 73 samples of ovarian carcinoma originating from 43 first-look laparotomies (FLL) and, in 30 cases, from secondary cytoreductions (SCR)(after chemotherapy) from the same patients. In paraffin sections immunohistochemical reactions were performed using antibodies directed to HER-2/neu, TOP 1A and Ki67. Kaplan-Meier's analysis disclosed a shorter overall survival time in cases with augmented expression of TOP 1A at FLL and with higher expression of Ki67 at SCR. A shorter progression-free time was detected in cases with higher proportion of Ki67 positive cells at FLL. No relationship could be disclosed between HER-2/neu expression and the studied clinicopathological parameters. The studies confirmed high value of Ki67 estimation. The augmented expression of TOP 1A was demonstrated to represent an unfavourable prognostic factor. Thus, in cases with elevated expression of TOP 1A application of topotecan-based therapeutic schemes should be considered.     

The Contrasting Role of p16Ink4A Patterns of Expression in Neuroendocrine and Non-Neuroendocrine Lung Tumors: A Comprehensive Analysis with Clinicopathologic and Molecular Correlations

Lung cancer encompasses a constellation of malignancies with no validated prognostic markers. p16^Ink4A expression has been reported in different subtypes of lung cancers; however, its prognostic value is controversial. Here, we sought to investigate the clinical significance of p16^Ink4A immunoexpression according to specific staining patterns and its operational implications. A total of 502 tumors, including 277 adenocarcinomas, 84 squamous cell carcinomas, 22 large cell carcinomas, 47 typical carcinoids, 12 atypical carcinoids, 28 large cell neuroendocrine carcinomas, and 32 small cell carcinomas were reviewed and subjected to immunohistochemical analysis for p16^Ink4A and Ki67. The spectrum of p16^Ink4A expression was annotated for each case as negative, sporadic, focal, or diffuse. Expression at immunohistochemical level showed intra-tumor homogeneity, regardless tumor histotype. Enrichments in cells expressing p16^Ink4A were observed from lower- to higher-grade neuroendocrine malignancies, whereas a decrease was seen in poorly and undifferentiated non-neuroendocrine carcinomas. Tumor proliferation indices were higher in neuroendocrine tumors expressing p16^Ink4A while non-neuroendocrine malignancies immunoreactive for p16^Ink4A showed a decrease in Ki67-positive cells. Quantitative statistical analyses including each histotype and the p16^Ink4A status confirmed the independent prognostic role of p16^Ink4A expression, being a high-risk indicator in neuroendocrine tumors and a marker of good prognosis in non-neuroendocrine lung malignancies. In this study, we provide circumstantial evidence to suggest that the routinary assessment of p16^Ink4A expression using a three-tiered scoring algorithm, even in a small biopsy, may constitute a reliable, reproducible, and cost-effective substrate for a more accurate risk stratification of each individual patient.     

The role of p21 Waf1/Cip1 in large airway epithelium in smokers with and without COPD

Airway epithelium alterations, including squamous cell metaplasia, characterize smokers with and without chronic obstructive pulmonary disease (COPD). The p21 regulates cell apoptosis and differentiation and its role in COPD is largely unknown. Molecules regulating apoptosis (cytoplasmic p21, caspase-3), cell cycle (nuclear p21), proliferation (Ki67/PCNA), and metaplasia (survivin) in central airways from smokers (S), smokers-COPD (s-COPD) and non-smokers (Controls) were studied. The role of cigarette smoke extracts (CSE) in p21, survivin, apoptosis (caspase-3 and annexin-V binding) and proliferation was assessed in a bronchial epithelial cell line (16HBE). Immunohistochemistry, image analysis in surgical samples and flow-cytometry and carboxyfluorescein succinimidyl ester proliferative assay in 16HBE with/without CSE were applied. Cytoplasmic and nuclear p21, survivin, and Ki67 expression significantly increased in large airway epithelium in S and in s-COPD in comparison to Controls. Caspase-3 was similar in all the studied groups. p21 correlated with epithelial metaplasia, PCNA, and Ki67 expression. CSE increased cytoplasmic p21 and survivin expression but not apoptosis and inhibited the cell proliferation in 16HBE. In large airway epithelium of smokers with and without COPD, the cytoplasmic p21 inhibits cell apoptosis, promotes cell proliferation and correlates with squamous cell metaplasia thus representing a potential pre-oncogenic hallmark.     

Ghrelin ovarian cell expression in patients with polycystic ovary syndrome: an immunohistochemical evaluation.

INTRODUCTION: The influence of ghrelin on different organs has been studied recently, e.g. in the regulation of pituitary hormone release, regulation of energy homeostasis, glucose metabolism and insulin secretion, cell proliferation, and reproductive function. However, the etiology of polycystic ovary syndrome has not been fully explained. The aim of our study was to estimate the presence of ghrelin in polycystic ovaries cells and evaluation of the relationship between ghrelin occurrence and cells proliferation. METHODS: In the present work we have compared ten polycystic ovaries with ovaries without pathology as the control group. We used immunohistochemical method to detect ghrelin. The cells proliferation was evaluated by Ki 67 proliferation index. RESULTS: Ghrelin immunostaining was demonstrated in cytoplasm of ovarian secondary interstitial cells and in atretic corpus luteum. The cell nuclei were ghrelin positive in granulosa, theca layers of follicular cyst in both groups as well as in luteal cells of young corpus luteum in healthy ovaries. Ki 67 immunostaining was observed in granulosa and theca layers of follicular cyst in polycystic and healthy ovaries. CONCLUSIONS: It is possible that local ghrelin expression plays an important role in the direct control of ovarian development and function and ghrelin may participate in patomechanism of PCOS.     

Stromal myofibroblasts in breast cancer: relations between their occurrence, tumor grade and expression of some tumour markers

It is suggested that tumour stromal myofibroblasts exert an unfavourable effect on the biology of breast cancer. We are aware of only a single study which examined relationships between manifestation of myofibroblasts in the stroma of breast cancer and clinicopathological data of the patients. The present study was aimed at estimation of the effect exerted by myofibroblasts present in the tumour stroma on principal pathological parameters and on expression of Ki67, P53 and HER-2 proteins in the group of the most frequent breast cancers, the ductal cancers. In paraffin sections of 60 ductal breast cancers (20 cases in G1, 20 in G2 and 20 in G3), immunohistochemical reactions were performed to detect expression of smooth muscle actin (SMA) in order to visualize myofibroblasts, Ki67, P53 and HER-2. The studies demonstrated that the most numerous myofibroblasts were present in G3 cases and they were the least frequent in G1 cases (P = 0.02). Positive correlations were observed between the presence of myofibroblasts in tumour stroma and expression of Ki67 and HER-2 in breast cancer cells in the entire group (P < 0.001 and P = 0.001, respectively), in G2 cases (P = 0.003 and P = 0.03) and in G3 cases (P = 0.01 and P = 0.03). Considering that the higher grade, Ki67 and HER-2 are thought to represent unfavourable prognostic factors, the elevated content of myofibroblasts in tumour stroma is probably typical for cases with worse prognosis.     

COX-2 is overexpressed in primary prostate cancer with metastatic potential and may predict survival. A comparison study between COX-2, TGF-β, IL-10 and Ki67

Background: The immune modulating molecules cyclooxygenase-2 (COX-2), transforming growth factor-β (TGF-β) and interleukin-10 (IL-10) have regulatory roles in cancer progression. There are conflicting data regarding the roles of these molecules in prostate cancer. To elucidate the prognostic impact of these proteins and provide information on prognosis and treatment, we compared the expression of COX-2, TGF-β, and IL-10 in prostate cancer specimens with or without metastases. Ki67 was included as a measure of growth fraction of tumor cells. Methods: Digital video analysis images from tumor cell areas and tumor stromal areas were analyzed on formalin fixed, paraffin-embedded and immunohistochemical stained cancer specimens from 59 patients: 32 patients with metastases and 27 patients without clinical, biochemical, or radiological evidence of metastases within 10 years after diagnosis. The expression of COX-2 was scored as negative, weak, moderate, or strong. The expressions of TGF-β and IL-10 were assessed as proportions of moderately or strongly stained cells. Ki67 was detected as strong nuclear staining in proliferating cells. Results: In primary cancers in the metastatic group, COX-2, TGF-β and Ki67 were stronger expressed in epithelial tumor cell and tumor stromal areas compared with non-metastatic cancers (for all markers, p < 0.0001). High intensity of COX-2 staining in tumor areas was strongly associated with death from prostate cancer in univariate analyses (hazard ratio [HR] 95% CI, 4.0 (1.1–14.5)). In multivariate analyses, the risk estimate was strengthened but did not reach significance. No associations to death were found for the other markers. Conclusion: High expression of COX-2, TGF-β and Ki67 were in metastatic primary prostate carcinoma compared to non-metastatic cancers. High expression of COX-2 was associated to death from prostate carcinoma.     

Prognostic Impact of Jab1, p16, p21, p62, Ki67 and Skp2 in Soft Tissue Sarcomas

Purpose

The purpose of this study is to clarify the prognostic significance of expression of Jab1, p16, p21, p62, Ki67 and Skp2 in soft tissue sarcomas (STS). Optimised treatment of STS requires better identification of high risk patients who will benefit from adjuvant therapy. The prognostic significance of Jab1, p16, p21, p62, Ki67 and Skp2 in STS has not been sufficiently investigated.

Experimental Design

Tissue microarrays from 193 STS patients were constructed from duplicate cores of viable and representative neoplastic tumor areas. Immunohistochemistry was used to evaluate the expression of Jab1, p16, p21, p62, Ki67 and Skp2.

Results

In univariate analyses, high tumor expression of Ki67 (P = 0.007) and Skp2 (P = 0.050) correlated with shorter disease-specific survival (DSS). In subgroup analysis, a correlation between Skp2 and DSS was seen in patients with malignancy grade 1 or 2 (P = 0.027), tumor size >5 cm (P = 0.018), no radiotherapy given (P = 0.029) and no chemotherapy given (P = 0.017). No such relationship was apparent for Jab1, p16, p21 and p62; but p62 showed a positive correlation to malignancy grade (P = 0.019). Ki67 was strongly positively correlated to malignancy grade (P = 0.001). In multivariate analyses, Skp2 was an independent negative prognostic factor for DSS in women (P = 0.009) and in patients without administered chemotherapy or radiotherapy (P = 0.026).

Conclusions

Increased expression of Skp2 in patients with soft tissue sarcomas is an independent negative prognostic factor for disease-specific survival in women and in patients not administered chemotherapy or radiotherapy. Besides, further studies are warranted to explore if adjuvant chemotherapy or radiotherapy improve the poor prognosis of STS with high Skp2 expression.     

Ki67在肿瘤中的表达及其临床指导意义

近年来,研究表明ki67的表达与很多肿瘤疾病的发生发展密切相关,如乳腺癌、卵巢癌、淋巴癌等。临床上,常通过免疫组化的方法检测ki67指数,反映正常和病变组织或细胞的增殖活性,对良、恶性肿瘤进行鉴别诊断,帮助恶性肿瘤的早期诊断、治疗方法选择和疗效的评估。但是,目前在临床和基础研究中,均无法以一个固定的ki67值判定不同肿瘤疾病的恶性程度,也无法以一个精确的ki67临界值判定肿瘤的恶性程度,有时更需要在治疗过程中对病患肿瘤组织的ki67指标进行跟踪检查来指导新的治疗及判断预后。本文主要就目前ki67指数与不同肿瘤的恶性程度、治疗效果及预后判断的关系进行了综述。     

Osteopontin in metastatic lesions as a prognostic marker in ovarian cancers

Summary Osteopontin (OPN) is expressed in various human cancers and associated with tumor progression, invasion and metastasis in many manners. The purpose of this study is to investigate the clinical significance of OPN expression in metastatic lesions of ovarian cancers, since the prognosis of the patients with peritoneal dissemination is extremely poor. In primary tumors and peritoneal metastatic lesions from 40 patients with stage III ovarian cancers, the protein levels of OPN and histoscores were determined by enzyme immunoassay and immunohistochemistry, respectively. Immunohistochemical staining revealed OPN was distributed in the cytoplasm and nuclear compartments of the cancer and stromal cells within and around the tumor. The OPN level was significantly (p < 0.05) increased in 32 of 40 metastatic lesions of ovarian cancers. The OPN increased cases identified by immunohistochemical staining were consistent with those identified by the sandwich immunoassay. The prognosis of the 32 patients with significant increase of OPN in ovarian cancers was extremely poor, whereas the 36-month survival rate of the 8 patients with no increase of OPN was 75%. Multivariate analysis revealed that the levels of OPN were independent predictors of prognosis from clinical characteristics (age, lesion size, histological types). OPN might be associated with peritoneal metastasis and its advancement, and that the OPN level in metastatic lesion may be a prognostic indicator in ovarian cancers.     

Relationship between the RB1 mRNA level and the expression of phosphorylated RB protein in human breast cancers: their relevance in cell proliferation activity and patient clinical outcome

The aim of the present study was to ascertain the relationship between the level of RB1 mRNA and the expression of phosphorylated RB protein and the relevance of these two parameters in cancer cell proliferation and clinical outcome in human breast cancer. Sixty-eight primary human breast cancers were considered. The amount of RB1 mRNA was evaluated by quantitative RT-PCR analysis. The level of RB phosphorylation was immunohistochemical defined by measuring the phosphorylated (pp) RB labelling index (LI). Cell proliferation rate was measured by calculating the Ki67 LI. No relation was found between the RB1 mRNA level and the ppRB LI (p=0.565). Both RB1 mRNA value and ppRB LI were related (in an inverse and direct manner, respectively) to Ki67 LI. RB1 mRNA expression was more strictly associated with KI67 LI (p=0.001) than the ppRB LI (p=0.013). Regarding the patient clinical outcome, the separately considered RB parameters did not reach the prognostic significance. However, patients with low RB1 mRNA quantity and patients with high ppRB LI, taken together, had a significantly shorter disease free and overall survival than the group comprehending patients with high RB1 mRNA value and low ppRB LI, and this despite the low number of patients considered. Our results demonstrated that the ppRB LI was independent of the RB1 mRNA level; that both RB parameters are related to the cell proliferation rate and, if collectively considered, have a high informative value on breast tumour prognosis.     

Quantum Dots-Based Quantitative and In Situ Multiple Imaging on Ki67 and Cytokeratin to Improve Ki67 Assessment in Breast Cancer

Background

As a marker for tumor cell proliferation, Ki67 has important impacts on breast cancer (BC) prognosis. Although immunohistochemical staining is the current standard method, variations in analytical practice make it difficult for pathologists to manually measure Ki67 index. This study was to develop a fluorescent spectrum-based quantitative analysis of Ki67 expression by quantum-dots (QDs) multiple imaging technique.

Methods

A QDs-based in situ multiple fluorescent imaging method was developed, which stained nuclear Ki67 as red signal and cytoplasmic cytokeratin (CK) as green signal. Both Ki67 and CK signals were automatically separated and quantified by professional spectrum analysis software. This technique was applied to tissue microarrays from 240 BC patients. Both Ki67 and CK values, and Ki67/CK ratio were obtained for each patient, and their prognostic value on 5-year disease free survival was assessed.

Results

This method simultaneously stains nuclear Ki67 and cytoplasmic CK with clear signal contrast, making it easy for signal separation and quantification. The total fluorescent signal intensities of both Ki67 sum and CK sum were obtained, and Ki67/CK ratio calculated. Ki67 sum and Ki67/CK ratio were each attributed into two grades by X-tile software based on the best P value principle. Multivariate analysis showed Ki67 grade (P = 0.047) and Ki67/CK grade (P = 0.004) were independent prognostic factors. Furthermore, area under curve (AUC) of ROC analysis for Ki67/CK grade (AUC: 0.683, 95%CI: 0.613–0.752) was higher than Ki67 grade (AUC: 0.665, 95%CI: 0.596–0.734) and HER-2 gene (AUC: 0.586, 95%CI: 0.510–0.661), but lower than N stage (AUC: 0.760, 95%CI: 0.696–0.823) and histological grade (AUC: 0.756, 95%CI: 0.692–0.820) on predicting the risk for recurrence.

Conclusions

A QDs-based quantitative and in situ multiple imaging on Ki67 and CK was developed to improve Ki67 assessment in BC, and Ki67/CK grade had better performance than Ki67 grade in predicting prognosis.     

p16和Ki67在非小细胞肺癌组织中的表达及其与预后的关系

目的探讨p16和Ki67在非小细胞肺癌（non-small cell lung cancer,NSCLC）中的表达,研究它们对NSCLC患者预后的影响及其与临床及病理因素之间的关系。方法收集NSCLC术后标本160例及正常肺组织20例（对照组）,应用免疫组化法检测NSCLC组织和正常肺组织中p16和Ki67的表达。结果在NSCLC组织和正常肺组织中,p16和Ki67的阳性表达率分别为23.8%、82.5%和90%、5%,差异有统计学意义（P〈0.05）。多因素分析：PTNM分期、淋巴结转移、p16及Ki67的表达是影响NSCLC根治术后患者预后的独立因素（P〈0.05）;p16阳性组与阴性组5年生存率分别为55.3%和18.0%,差异有统计学意义（P〈0.05）;Ki67阳性组与阴性组5年生存率分别为23.5%和42.9%,差异有统计学意义（P〈0.05）,p16和Ki67表达呈负相关（P〈0.05）。结论 p16和Ki67参与了NSCLC的发生发展,p16和Ki67的表达水平与NSCLC的发展及预后有一定的关系。     

Possible prognostic significance of p53 and Ki 67 in inverted sinonasal papilloma

The aim of this study is to test the possible prognostic significance of p53 and Ki67 expression in inverted papilloma of the lateral nasal wall and adjacent sinuses regarding their malignant potential and recurrence. 49 biopsies of the lateral nasal wall and adjacent sinuses obtained from 41 patients from three hospitals were investigated. Immunohistochemically demonstrated p53 and Ki67 expression was measured and statistically evaluated. p53 immunoreactivity was demonstrated in most of papillomas with carcinomas but only in two benign papillomas, while Ki67 demonstrated stronger immunoreactivity in carcinomas and surrounding epithelium. Immunohistochemical staining of inverted sinonasal papillomas for p53 and Ki67 can give useful information concerning the existence of synchronous carcinoma and, in case of high Ki67, a hint toward possible recurrence.     

Impaired follicle development and infertility in female mice lacking steroidogenic factor 1 in ovarian granulosa cells

The nuclear receptor steroidogenic factor 1 (SF-1 [officially designated NR5A1]) is essential for fetal gonadal development, but its roles in postnatal ovarian function are less well defined. Herein, we have extended our analyses of knockout (KO) mice with markedly decreased SF-1 expression in granulosa cells. As described, these SF-1 KO mice had hypoplastic ovaries that contained a decreased number of follicles and lacked corpora lutea. In the present study, we showed that SF-1 KO mice exhibited abnormal estrous cycles, were infertile, and released significantly fewer oocytes in response to a standard superovulation regimen. Moreover, they had blunted induction of plasma estradiol in response to gonadotropins. The granulosa cell-specific SF-1 KO also significantly affected ovarian expression of putative SF-1 target genes. Consistent with their decreased follicle number, these mice had reduced ovarian expression of anti-müllerian hormone (Amh), which correlates with the reserve pool of ovarian follicles, as well as decreased gonadotropin-induced ovarian expression of aromatase (Cyp19a1) and cyclin D2 (Ccnd2). In contrast, perhaps because of their abnormal cyclicity, SF-1 KO ovaries had higher basal expression of inhibin-alpha. They also had decreased immunoreactivity for genes related to proliferation (Ccnd2 and Mki67 [also known as Ki67]) and increased expression of Cdkn1b, also known as p27, which inhibits cyclin-dependent kinases, arguing for a role of SF-1 in granulosa cell proliferation. These findings demonstrate that SF-1 has a key role in female reproduction via essential actions in granulosa cells.     

Expression of proliferation marker Ki67 correlates to occurrence of metastasis and prognosis, histological subtypes and HPV DNA detection in penile carcinomas

Clinical outcome of penile squamous cell carcinoma (PSCC) largely depends on the presence of lymph node metastasis. In search of a valuable marker predicting the risk for metastasis, the expression of Ki67 was investigated immunohistochemically in primary tumors and compared to presence of inguinal lymph node metastasis. As human papilloma virus (HPV) is thought to affect Ki67 expression, we evaluated whether occurrence of HPV DNA correlates to Ki67 score or metastatic potential. Samples originated from patients subjected to resection of invasive SCC of penis. Immunohistochemistry was done on paraffin-embedded sections using a monoclonal antibody against Ki67. After DNA isolation from paraffin embedded tissue the presence of HPV 6/11, HPV 16 and HPV 18 DNA was analyzed by PCR. Statistical analysis was done using two tail unpaired t test and Chi-square test. Four of 28 patients showed a weak Ki67 expression, without displaying lymph node metastasis. Among 17 patients showing an intermediate Ki67 index, eight exhibited metastases while in all seven patients with a strong expression of Ki67 lymph node metastases were found. The median Ki67 expression in metastastic lesions was significantly different (50.3%) from tumors without lymph node metastasis (31.8%) (p=0.024). Furthermore, a correlation between presence of HPV DNA and strong Ki67 expression was determined (p=0.009). Since our study demonstrated a strong Ki67 labeling index significantly associated to positive lymph nodes, we suggest Ki67 expression as a prognostic marker for lymph node metastasis in penile squamous carcinoma.     

Immunohistochemical profile of ovarian inclusion cysts in patients with and without ovarian carcinoma

Summary The expression of cytokeratin, epithelial membrane antigen, Leu-M1, B72.3, carcinoembryonic antigen, human placental lactogen, proliferating cell nuclear antigen, p53, and ovarian carcinoma-associated antigen OC-125 was evaluated in inclusion cysts in contralateral ovaries of patients with unilateral ovarian carcinoma. The findings were compared with the findings in inclusion cysts in ovaries of patients without ovarian carcinoma. Although there was more frequent expression of tumour markers B72.3 and CEA in patients with ovarian carcinoma, these differences did not reach statistical significance.     

Co-Expression of p16, Ki67 and COX-2 Is Associated with Basal Phenotype in High-Grade Ductal Carcinoma In Situ of the Breast

We assessed the co-expression of cell cycle-related biomarkers in a series of 121 consecutive cases of high-grade ductal carcinoma in situ (DCIS), pure or associated with invasive carcinoma, and their associations with the different immunoprofiles of DCIS. Cases were identified from the histopathology files of the Breast Pathology Laboratory, Federal University of Minas Gerais, Brazil, from 2003 to 2008. The expression of estrogen receptor, progesterone receptor, HER2 overexpression, cytokeratin 5, epidermal growth factor receptor 1, cyclooxygenase-2, p16 and Ki67 were assessed. Tumors were placed into five subgroups according to their immunohistochemical profile: luminal A, luminal B, HER2, basal-like and “not classified”. We found that the basal phenotype was associated with a higher frequency of p16-positive cases (83%) and the luminal A phenotype showed a higher frequency of p16-negative cases (93%; p=0.000). The association of biomarkers p16⁺/Ki67⁺/COX2⁺ was expressed in 02/06 cases (33.3%) of the basal phenotype but in only 01/70 cases (1.4%) of the luminal A phenotype (p=0.01). The co-expression of p16⁺/Ki67⁺/COX2^- was associated with a basal phenotype (p=0.004). P16 expression, p16⁺/Ki67⁺/COX2⁺ and p16⁺/Ki67⁺/COX2^- co-expression showed significant associations with the basal phenotype and these profiles could be used to guide more aggressive treatment strategies in patients with high-grade DCIS.     

上皮性卵巢癌患者组织P53、Ki67表达及其临床意义

摘要 目的：探讨上皮性卵巢癌患者组织P53、Ki67表达及其临床意义。方法：选择卵巢肿瘤102例,其中病理诊断为良性卵巢肿瘤40例(良性组)和上皮性卵巢癌62例(恶性组),采用免疫组化法检测组织P53、Ki67表达水平,调查患者的临床病理特征并进行相关性分析。结果：恶性组的P53、Ki67表达阳性率为80.6 %和72.6 %,显著高于良性组的10.0 %和12.5 %(P<0.05)。在恶性组中,不同浸润转移、分化程度、病理分期患者的P53、Ki67表达阳性率对比差异有统计学意义(P<0.05)。直线相关分析显示上皮性卵巢癌患者P53表达阳性率与Ki67表达阳性率呈现显著正相关性(r=0.872,P=0.000)。多因素logistic回归分析显示浸润转移、分化程度、病理分期都为影响P53、Ki67表达阳性率的主要因素(P<0.05)。结论：上皮性卵巢癌患者组织P53、Ki67都呈现高表达状况,与患者的临床病理特征显著相关,两者也可互相影响,共同参与上皮性卵巢癌的发生与发展。     

Prognostic prediction of the immunohistochemical expression of p16 and p53 in cutaneous melanoma: a comparison of two populations from different geographical regions

p16INK4a and p53 are tumor-suppressor genes frequently altered in various malignancies, including cutaneous melanoma. The purpose of the study was to establish the prognostic value of immunohistochemical expression of p16INK4a a and p53 in sporadic cutaneous melanoma (CM) in two regions with a high-risk for melanoma in Italy and Ecuador. Immunohistochemical staining of p16 and p53 was performed in samples of primary CM from 82 patients with Stage I and II melanoma according to the American Joint Committee on Cancer (AJCC) staging system. Survival differences between categories of p16 or p53 expression were analyzed using the product-limit procedure (Kaplan-Meier method, log-rank test). Clinical variables (gender, age, tumor location, Clark's level, thickness) were correlated with survival and p16 or p53 expression. p16 nuclear immunoreactivity was observed in 85% of Italian patients compared to 48.7% of Ecuadorians; a small number of cases showed p53 immunoreactivity in both populations. Only nuclear p16 expression exhibited a significant correlation with survival (Italians p=0.001, Ecuadorians p=0.017) but did not appear to correlate with any clinicopathological parameter. No significant difference was observed in survival with regard to p53 expression or cytoplasmic p16. Our results demonstrate that nuclear expression of p16 can be considered a molecular prognostic factor in patients with sporadic CM and indicate its importance as a clinical marker.