Tumor angiogenesis as a prognostic factor in thick cutaneous malignant melanoma

The prognostic value of the extent of neovascularization in cutaneous melanoma is a highly controversial issue. The aim of the current study was to evaluate whether the morphometric analysis of tumor vascularity may be helpful in predicting the clinical outcome of patients with thick cutaneous melanomas. A series of 15 patients with melanoma (>3 mm in thickness) who did not experience disease progression after long-term follow-up (10 years) and 30 matched controls who underwent recurrence and/or metastases were selected for the study. Microvessels were immunohistochemically stained with anti-CD31 antibody. Several parameters, including vessel number, vascular density, vessel area, equivalent circle diameter, perimeter, shape factor, compactness, and the number of vascular ramifications per 100 vessel sections, were quantitatively assessed by a computer-aided semi-automatic image analysis system. Mean vessel area was 341.69 microm2 in cases without progression and 512.55 microm2 in the progressed melanomas (P=0.008, Mann-Whitney U test). The mean equivalent circle diameter was 18.95 microm in non-progressed melanomas and 22.57 microm in progressed melanomas (P=0.009). The mean number of ramifications was 0.8 in cases without progression and 1.9 in the controls (P=0.03). Microvessel count and vascular density were higher in progressed cases (17.37 vs. 11.73 and 28.94/mm2 vs. 19.55/mm2, respectively), but the difference did not reach statistical significance (P=0.06). Our results suggest that neovascularization is a critical event in the progression of thick melanoma. Its prognostic significance is better assessed by quantification of vessel area, equivalent circle diameter, and microvessel branching, whereas microvessel count and vascular density do not provide significant prognostic information.     

A prognostic index in skin melanoma through the combination of matrix metalloproteinase-2, Ki67, and p53

The objective of this immunohistochemical study was to explore the roles of Ki67 and p53 in conjunction with matrix metalloproteinase-2 and matrix metalloproteinase-9, tissue inhibitors of metalloproteinase-1 and tissue inhibitors of metalloproteinase-2 in a series of 157 cases of skin melanomas. Elevated Ki67 expression and positive staining for p53 correlated to the propensity to metastasize (P = .016) and to declined disease-specific survival, as well as to shortened recurrence-free survival. In patients with a high immunoreaction for Ki67, the 10-year disease-specific survival was 39% compared with 73% in patients with a low Ki67 expression (P = .03). In cases with a positive p53 expression in melanoma cells, the 10-year disease-specific survival was 59% compared with 76% in patients with a negative immunoreaction for p53 (P = .005). Overexpression of the matrix metalloproteinase 2 protein in conjunction with overexpression of Ki67 characterized melanomas with high metastatic potential and was associated with declined survival with a 10-year disease-specific survival of 33% compared with 85% in the cases with low matrix metalloproteinase-2 and low Ki-67 levels (P = .002). Similarly, in cases with overexpression of matrix metalloproteinase-2 and a positive immunoreaction for p53, the 10-year disease-specific survival was only 42% compared with 80% in patients with matrix metalloproteinase-2 less than 20% and a negative immunostaining for p53 (P < .001). The presence of all 3 adverse prognostic factors was prognostically more significant than any marker alone with a 10-year survival of only 28%. This combination of determining matrix metalloproteinase 2, Ki67, and p53 immunoreactive proteins could be beneficial in the selection of high-risk melanoma patients for future adjuvant trials.     

Expression of p16 in sinonasal malignant melanoma

The aim of this study was to investigate the expression of p16 in relation with the histopathologic features and the clinical course in patients with sinonasal melanoma. Thirty-seven sinonasal melanomas were immunostained for p16. Seventeen tumours were investigated for loss of the 9p21 region using interphase fluorescence in situ hybridization (FISH). Twenty-seven melanomas (72.9%) showed loss of p16 expression. All cases with spindle or mixed cytology showed loss of p16, whereas this was present in 50% of epithelioid tumours (p=0.01). Loss of p16 expression was more frequently seen in melanomas with alveolar architecture (87.5%) than in tumours with diffuse architecture (68.9%) (p=0.4). There was no correlation between p16 expression and presence of lymph node or distant metastases (p=0.57 and 0.24, respectively). In addition, p16 status did not influence overall survival (p=0.2). The FISH results were in good agreement with immunohistochemistry: 11 tumours out of 17 showed deletion of the 9p21 region and 10 of these showed loss of protein expression. Loss of p16 expression is a frequent event in sinonasal melanoma and it is mainly related to deletion of 9p21 region. At variance from cutaneous melanoma, loss of p16 is not correlated with the prognosis of patients affected by sinonasal melanoma.     

Mucosal malignant melanoma – a clinical,oncological, pathological and genetic survey

Mucosal melanomas constitute 1.3% of all melanomas and they may develop in any mucosal membrane. Conjunctival melanomas (0.5/million/year) and melanomas in the sinonasal cavity (0.5/million/year) are the most common, followed by anorectal melanomas (0.4/million/year) and melanomas in the oral cavity (0.2/million/year). Anorectal melanoma occurs slightly more often in females, whereas oral melanoma has a male predilection. Mucosal melanoma most commonly develops in a patient's sixth or seventh decade of life, and no differences between races have been found except for sinonasal melanoma and conjunctival melanoma, which are very rare in Black people. The symptoms are not tumour‐specific and are related to the organ system affected, and the disease is most often diagnosed at an advanced clinical stage. The diagnosis of a primary tumour is difficult, and metastatic cutaneous melanoma and choroidal melanoma must be excluded. Mutations in KIT are frequently found, while BRAF and NRAS mutations are rarely found – except in conjunctival melanomas that carry BRAF mutations. Mutations in the TERT promotor region are also found in mucosal melanomas. Complete surgical resection with free margins is the treatment of choice. The prognosis is poor, with the 5‐year survival rate ranging from 0% (gastric melanoma) to 80% (conjunctival melanoma).     

Immunolocalisation studies of matrix metalloproteinases-1, -2 and -3 in human melanoma

The matrix metalloproteinases (MMPs) are considered to have an important role in connective tissue degradation and have been implicated in the mechanisms of tumour invasion and metastatic spread. We have used immunohistochemistry to examine and compare the tissue distributions of collagenase-1 (MMP-1), gelatinase A (MMP-2) and stromelysin-1 (MMP-3) in 18 specimens of malignant melanoma, viz. 10 superficial spreading and 8 nodular melanomas. MMPs-1, -2 and -3 were demonstrated within melanoma and host tissue cells, especially at the periphery of some tumours, but were usually restricted to less than 10% of total melanoma cells. The MMPs were absent from ’normal’ skin tissue distant from the tumour. MMP-2 was localised to discrete groups of cells and was especially evident at the epidermal:tumour interface, whereas MMP-3 was mainly confined to the deeper margins of melanoma. No regular pattern of MMP expression was observed for either the superficial spreading or the nodular melanomas. The variable distributions of the MMPs suggested that enzyme expression was subject to local microenvironmental regulation, possibly in response to matrix components and the cellular heterogeneity observed at the tumour margins. These in situ observations add weight to the concept that specific MMPs contribute to the mechanisms of tumour invasion. Received: 10 March 1999 / Accepted: 6 July 1999     

MMP-9 is predominantly expressed in epithelioid and not spindle cell uveal melanoma

Extracellular matrix-degrading enzymes are crucial for cancer metastases. One group of enzymes that has been increasingly implicated in the breakdown of the extracellular matrix, and hence the intravasation and dissemination of tumour cells, is the family of metalloproteinases. In the recent past, increasing efforts have led to the development of more or less specific matrix metalloproteinase (MMP) inhibitors. Data concerning the molecular nature and timing of the contribution of MMPs to tumour spread is of paramount importance in clarifying which MMP is an appropriate target for more selective MMP inhibition in future tumour therapy. This study immunohistochemically characterized the expression pattern of MMP-2, -3, and -9 in 26 uveal melanomas. Forty-six per cent of the uveal melanomas expressed MMP-2 and/or MMP-9. MMP-3 expression was seen in 17 out of 26 uveal melanomas. MMP-9, previously shown to play an important part in tumour dissemination, was predominantly present in epithelioid melanomas (71.4%) or the epithelioid portion of mixed cell uveal melanomas (67%), whereas only one out of ten spindle cell melanomas showed MMP-9 expression (10%). MMP-2 and MMP-9 expression was associated with a significantly higher incidence of metastatic disease. The survival rate of patients with MMP-2-positive melanomas was 31% vs. 85% for patients with MMP-2-negative (p<0.05); for MMP-9-positive uveal melanomas the survival rate was 27% vs. 85% with MMP-9-negative uveal melanomas (p<0.04). The fact that patients suffering from TIMP-1- as well as TIMP-2-positive uveal melanomas tended to show a better survival rate (72% vs. 45% for TIMP-1; 88% vs. 37% for TIMP-2) supports the view that proteolytic enzymes are of importance in tumour spread.     

非小细胞肺癌患者p53蛋白和MMP2表达水平与同步放化疗的相关性

目的 研究非小细胞肺癌(NSCLC)患者p53蛋白、MMP2的表达与同步放化疗疗效的相关性.方法 选取2013年2年至2014年1月在我院接受同步放化疗的NSCLC患者89例.采用免疫组化方法检测患者组织中P53蛋白的表达情况,并根据P53蛋白表达与否分为阳性组(41例)与阴性组(48例).分别比较两组患者的疗效、生存率及治疗前后血清MMP2的表达,并进行相关性分析.结果 阳性组患者RR为53.66%(22/41),显著低于阴性组的75.00%(36/48),P<0.05差异有统计学意义.治疗后阴性组MMP2水平为60.9±23.4μg/mL,显著低于阳性组的75.5±31.7μg/mL,P<0.05差异有统计学意义.阳性组平均生存期为17.3±4.6月,显著低于阴性组的31.4±5.3月,差异有统计学意义(t=12.865,P<0.001).经Spearman相关性分析可得,NSCLC患者组织p53蛋白表达、血清MMP2的表达与同步放化疗疗效及生存期均呈显著负相关.结论 NSCLC患者p53蛋白、血清MMP2的表达与同步放化疗疗效均呈显著负相关,且与生存期也呈显著负相关,对治疗NSCLC具有参考价值.     

Tenascin-C in primary malignant melanoma of the skin

AIMS: To investigate the expression and the prognostic role of glycoprotein Tenascin-C (Tn-C) in primary melanoma of the skin. METHODS AND RESULTS: The immunohistochemical expression of Tn-C was studied in 98 primary melanomas and related to inflammation, invasion, and patient outcome. Patients were followed up for disease recurrence for 0.04-7.4 years (median 3.9) and for survival for 0.5 to 12.1 years (median 9.3). The expression of Tn-C was evaluated for each tumour invasion border; the stromal and intracytoplasmic Tn-C of the melanoma islets were also recorded. Tn-C is widely expressed in primary melanoma samples, the staining pattern varying from focal to diffuse in different parts of the tumour. No correlation existed between intensity of Tn-C staining and inflammation. No stromal Tn-C was detected at the upper dermal lateral border in 12 patients, nor at the deep, dermal or subcutaneous border in 14 patients. These patients showed better disease-free survival (DFS) than did those cases with focal or diffuse staining (P = 0.06, P = 0.05). Also, absence of intracytoplasmic Tn-C was a beneficial prognostic factor for DFS (P = 0.04). In multivariate analysis, tumour ulceration and intracytoplasmic Tn-C expression of melanoma cells were independent adverse prognostic factors for DFS. CONCLUSIONS: In primary melanoma of the skin, absence of Tn-C in the stroma of invasion fronts and within tumour cells seems to be related to a more benign disease behaviour with a lower risk of developing metastases.     

Comparison of the prognostic value of matrix metalloproteinases 2 and 9 in cutaneous melanoma

Previously, gelatinases matrix metalloproteinase (MMP)-2 and MMP-9 have been shown to be involved in melanoma invasion and progression. Also, overexpression of MMP-2 has been suggested to be linked to hematogenous metastasis in melanoma. This study was conducted to study the prognostic value of MMP-2 and MMP-9 in human melanoma. The expression of MMP-2 and MMP-9 immunoreactive protein was evaluated in 157 cases of primary melanomas. An immunohistochemical analysis using specific monoclonal antibodies for MMP-2 and MMP-9 on paraffin-embedded tissues was performed, and the immunostaining results were compared with the clinical course of melanoma. Overexpression of MMP-2 (>20% of malignant cells positive) was an independent prognostic marker for melanoma related death, with odds ratio of 2.6 (95% confidence interval, 1.32-5.07). The 10-year disease-specific survival rate was only 51% in patients with overexpression of MMP-2 protein compared with 79% in patients with a primary melanoma with low expression for MMP-2 (P = .001). Interestingly, male patients with a melanoma with overexpression of MMP-2 showed a 10-year disease-specific survival of only 41% compared with 77% in other male patients (P = .003). It is notable that the immunoreactive protein for MMP-9 in primary melanoma was not found to be of any prognostic importance. In the future, MMP-2 could be acknowledged as a new prognostic factor in melanoma. MMP-9, on the other hand, was not associated with the clinical course of melanoma. Based on the current data, MMP-2 could be evaluated as an inclusion factor for adjuvant studies especially in male melanoma patients.     

Solar elastosis in cutaneous melanoma

By studying more than 1,200 patients with cutaneous melanoma and long-term follow-up, I examined the relationship between solar elastosis and age at diagnosis of melanoma, key features of melanoma, and the outcome of overall survival in melanoma. I found that melanomas with elastosis were diagnosed significantly later than those without elastosis (P approximately 0; log-rank test). This result may be because elastosis is positively related to age. However, I also found that melanomas of head and neck areas, which tend to have more elastosis, were diagnosed at later ages than melanomas of other body sites (P = 1.2 x 10-5; log-rank test). Thus, a second explanation for the results favors a protective effect of elastosis on the development of cutaneous melanoma, possibly related to increased levels of vitamin D. I also found that once melanoma develops, cases with elastosis demonstrated no differences in thickness, mitotic rate, ulceration, or overall survival time from cases without elastosis.     

Expression and role of matrix metalloproteinases MMP-2 and MMP-9 in human spinal column tumors

Matrix metalloproteinases (MMPs) have been implicated in the process of tumor invasion and metastasis formation. Thus, we determined the expression of MMPs in various primary and metastatic spinal tumors in order to assess the role of these enzymes in spinal invasion. MMP expression was examined by immuno-histochemical localization, and quantitative evaluation of MMP protein content was determined by enzyme-linked immunosorbant assay (ELISA) and Western blotting. MMP enzyme activity was determined by gelatin zymography. Lung carcinomas and melanomas metastatic to the spine were shown to have higher levels of MMP-9 activity than those of breast, thyroid, renal metastases and primary spinal tumors. Immunohistochemical analysis revealed similar difference in expression of MMP-9 in tissue samples. When the tissue samples were subjected to gelatin zymography for examination of MMP-2 and MMP-9 activity and to ELISA and Western blotting for quantitative estimation of protein content, the most striking results were obtained for lung carcinomas and melanomas relative to the other tumors. Lung carcinomas and melanomas metastatic to the spine had considerably higher levels of MMP-9 activity than those of primary spinal tumor or breast, thyroid, and renal carcinoma metastases. Within the metastatic tumor category, neoplasms that are known to be associated with the shortest overall survival rates and most aggressive behavior, such as lung carcinomas and melanomas, had the highest levels of MMP-2 and MMP-9 activity compared to those less aggressive metastatic tumors such as breast, renal cell, and thyroid carcinomas. Our results suggest that MMPs may contribute to the metastases to the spinal column, and overexpression of these enzymes may correlate with enhanced invasive properties of both primary and metastatic spinal tumors.© Kluwer Academic Publishers 1998     

Membrane-type-1 matrix metalloproteinase, matrix metalloproteinase 2, and tissue inhibitor of matrix proteinase 2 in prostate cancer: identification of patients with poor prognosis by immunohistochemistry

Overexpression of the matrix metalloproteinase (MMP) 2 is associated with poor prognosis in many tumor types. Membrane-type-1 MMP (MMP14) activates MMP2 using pro-MMP2 specific inhibitor, tissue inhibitor of matrix proteinase 2 (TIMP2), as a receptor. We evaluated, by immunohistochemistry on 189 T3N0-2M0 prostate cancer (Pca) cases, the influence of MMP2, MMP14, and TIMP2 expression, individually and in association, on Pca disease-free survival (DFS). We evaluated marker expression separately in cancer, stromal, and benign epithelial (BE) cells according to a percentage scale (0%, <10%, 10%-50%, and >50%). Median follow-up was 4.61 years. In BE cells, there was an inverse relationship between initial prostate-specific antigen serum level and T3 stage with MMP14 expression (P = .003) and between pN stage and TIMP2 expression (P = .04). The most significant results with survival were obtained by dichotomizing the cases between those with less than 10% and at least 10% of cells expressing the marker, the latter category representing overexpression. TIMP2 overexpression in stromal cells was associated with a longer DFS with a hazard ratio of 0.573 (P = .02) for time to recurrence. MMP2 overexpression by BE cells correlated with a shorter DFS using a multivariate trend test (hazard ratio = 1.46, P = .02). Stromal cells expressing less than 10% TIMP2 and MMP2 overexpression was the only combination that was significantly associated with a shorter DFS (log-rank test, P = .0001). This study suggests that MMP14 is involved mostly in Pca implantation and that MMP2 and TIMP2 expression by reactive stromal cells might be used as predictors of DFS in T3N0-2M0 Pca.     

Activation of c-jun N-terminal kinase is associated with cell proliferation and shorter relapse-free period in superficial spreading malignant melanoma.

Signaling pathways regulating cell proliferation and survival have become attractive targets for anticancer strategies. In the present study, we analyzed by immunohistochemistry, a panel of benign nevi, superficial spreading and nodular primary melanomas and metastases for expression of activated p38/mitogen-activated protein kinase (p-p38) and c-jun N-terminal kinase (JNK) (p-JNK) and correlated the findings with known prognostic variables. Twenty-five and 35% of the primaries and 9 and 25% of the metastases expressed variable levels of p-p38 and p-JNK, respectively. In benign nevi, 73.5% expressed p-JNK and 7% expressed p-p38. For patients with superficial spreading melanomas, high level of cytoplasmic p-JNK was associated with thicker tumors (P=0.017) and shorter disease-free survival (P=0.003) as well as with markers of cell proliferation (cyclin A (P=0.017) and p21 (P=0.021)). In nodular melanomas, nuclear p-p38 was associated with Ki-67 (P=0.012), but neither cytoplasmic nor nuclear localized p-p38 was associated with disease outcome. Of note, in superficial spreading melanomas, a positive correlation between cytoplasmic p-JNK and cytoplasmic p-extracellular signal-regulated kinase ERK(1/2) (P=0.005) and p-p38 (P=0.003) was observed. Likewise, p-p38 in cytoplasm was positively associated with cytoplasmic p-ERK1/2 (P<0.0005) and p-Akt (P=0.047). In contrast, except for a positive correlation between nuclear p-p38 and membranous p-TrkA (P=0.02), no correlation between the activation status of the different signaling pathways was observed in nodular melanomas. In conclusion, our results suggest that in benign nevi activated JNK may have a role in restricting uncontrolled cell proliferation or survival. However, during tumor progression, activation of JNK is associated with cell proliferation and shorter relapse-free period for patients with superficial spreading melanomas, suggesting that the JNK activation status could be a marker for clinical outcome in at least a subgroup of malignant melanoma. In contrast, activation of p38 seems to play a less important role in development and progression of malignant melanomas.     

Expression of activated TrkA protein in melanocytic tumors: relationship to cell proliferation and clinical outcome

We evaluated expression of activated nerve growth factor receptor tyrosine kinase (p-TrkA) by immunohistochemical analysis in 152 primary and 64 metastatic human melanoma biopsy specimens and 8 nevi. Membranous, cytoplasmic, and/or nuclear expression of p-TrkA was seen in 54.6% of primary melanomas and 30% of metastases. Membranous p-TrkA was detected in 21.7% of primary and 14% of metastatic melanomas and cytoplasmic immunoreactivity in 28.9% of primary tumors and in 22% of metastases. Significantly fewer metastases than primary tumors expressed nuclear p-TrkA (16% vs 39.5%; P = .006). A significantly higher percentage of nodular than superficial spreading melanomas expressed membranous (40% vs 11%; P < .0001) p-TrkA. Nevi expressed no membranous or cytoplasmic p-TrkA; 63% showed nuclear reactivity. p-TrkA expression varied significantly with thickness of primary tumors (lower expression in thinner lesions: membranous, P = .004; cytoplasmic, P = .001; nuclear, P = .031). An association between ulceration and membranous (P = .054), cytoplasmic (P < .0001), and nuclear (P = .022) p-TrkA expression was found. Membranous p-TrkA significantly predicted decreased overall survival (P = .002). A significant association between membranous p-TrkA and cyclin A (P = .004) and Ki-67 (P < .0001) and between cytoplasmic p-TrkA and cyclin A (P < .0001), Ki-67 (P = .004), and cyclin D3 (P = .027) was found. p-TrkA had no effect on MAPK(ERK1/2) activation. A significant inverse association between cytoplasmic beta-catenin and cytoplasmic p-TrkA levels (P = .006) and between nuclear p-TrkA and cytoplasmic E-cadherin (P = .022) was seen. We present the first evidence of a role for TrkA activation in a subset of melanomas as a predictor of an aggressive phenotype and poor outcome.     

Malignant melanoma in the oral region: ultrastructural and immunohistochemical studies

Malignant melanoma in the oral region is reviewed in its clinicopathological aspects. Clinically the melanomas were classified into five types; however, there were no histopathological differences according to these clinical types. Electron microscopic observation of the melanomas and primary culture cells derived from oral malignant melanoma revealed that, in patients whose prognoses were relatively good, many mature-stage melanosomes were found. Immunohistologically, there was a positive reaction for transferrin receptor and the expression of pRb2/p130 was found in only 2 of 13 patients, who are still alive after periods of over 14 years. The radiosensitivity of a cell line derived from human oral malignant melanoma was greater than that in cell lines derived from human cutaneous melanoma and with radiation, the number of melanosomes increased. There are very few clinical cases of oral malignant melanoma and very few cell lines derived from oral malignant melanoma, and so findings in these patients and these cell lines should be accumulated in order to clarify the biological behavior of oral malignant melanoma.     

Sinonasal malignant melanoma. A clinicopathologic and immunohistochemical study of 14 cases.

The clinical, light microscopic, and immunohistochemical features of 14 sinonasal malignant melanomas were studied to show their diverse morphologic appearance and distinction from therapeutically more amenable neoplasms that occur in this region. The tumors arose in 6 men and 8 women (median age, 70 years). Eleven patients died of disease 7 to 44 months (median, 18 months) after diagnosis. The absolute median survival time was 18.5 months (range, 7 to 44 months). The predominant microscopic appearance was categorized as small blue cell in eight cases, spindle cell in three cases, epithelioid in two cases, and pleomorphic in one case. Eight tumors had multiple patterns. Five sinonasal malignant melanomas had theque-like growth, five had junctional change, and 10 contained at least rare melanin pigment. Fourteen, 13, and 12 sinonasal malignant melanomas were immunoreactive with anti-vimentin, HMB45, and anti-S100 protein antibodies, respectively. One epithelioid tumor positive for vimentin, S100, and HMB45 also contained scattered epithelial membrane antigen-positive and cytokeratin-positive cells, which emphasizes the need for a battery of stains to distinguish sinonasal malignant melanoma from carcinoma. All tumors were negative for leukocyte common antigen, muscle-specific actin, and synaptophysin. Diffuse immunopositivity for vimentin, S100 protein, and HMB45 allows distinction of sinonasal malignant melanomas from histologically similar neoplasms.     

bFGF和MMP9在鼻咽癌组织中的表达及其临床意义

目的:探讨碱性成纤维细胞生长因子(bFGF)和基质金属蛋白酶9(MMP9)在鼻咽癌患者中的表达及其临床意义。方法:应用免疫组化方法检测289例鼻咽癌患者活检组织治疗前bFGF和MMP9的表达水平,并分析二者与鼻咽癌患者临床病理特征和预后的关系。结果:289例鼻咽癌组织bFGF和MMP9阳性表达率分别为71.3%和61.6%;bFGF和MMP9的阳性表达与鼻咽癌的N分期和临床分期有显著的相关性(P0.05),且两者的高表达均与鼻咽癌的不良预后显著相关(P0.01);在鼻咽癌组织中Spearman相关分析发现,bFGF的表达与MMP9的表达呈明显正相关(r=0.634,P0.05);亚组分析表明,bFGF和MMP9表达水平均升高的鼻咽癌患者的预后最差。结论:bFGF和MMP9在鼻咽癌组织中的表达升高,且两者与鼻咽癌的不良预后明显相关,联合应用有可能成为鼻咽癌的诊断、治疗及判断预后的生物标志物。     

Abnormal expression of matrix metalloproteinase-9 (MMP9) correlates with clinical course in Chinese patients with endometrial cancer

Aims and background: The aim of the present study was to analyze the expression of matrix metalloproteinase-9 (MMP9) in endometrial cancer and its correlation with clinicopathologic features in Chinese patients, including the survival of patients with endometrial cancer. Methods: Using immunohistochemistry analysis, we analyzed MMP9 protein expression in clinicopathologically characterized 128 endometrial cancer (EC) cases with age ranging from 30 to 85 years (median=51.6 years) and 30 endometrial atypical hyperplasia (EAH) and 30 normal endometrium (NE). Cases with greater than or equal to 6 and less than 6 with the score value of cytoplasmic MMP9 immunostaining were regarded as high expression and low expression, respectively. The relationship between the expression levels of MMP9 and clinical features was analyzed in EC cases. Results: Immunohistochemical analysis revealed that the protein expression of MMP9 detected in EC tissues was higher than that in the EAH tissues and NE tissues (P=0.006). In addition, high levels of MMP9 protein were positively correlated with the status of lymph node metastasis (P=0.044) and the histopathological grade (P<0.05) of EC patients. Patients with higher MMP9 expression did not correlate with EC patients'' clinical outcome in China. Multivariate analysis suggested that status of lymph node metastasis and depth of myometrial invasion, but not MMP9 expression level, were significantly correlated with patients'' survival. Conclusion: MMP9 is highly expressed in ECs and correlates with the progression of ECs, but not be helpful in predicting the prognosis of EC patients.