Expressão da proteína nm23 em carcinoma de células escamosas de língua metastático e não-metastático / nm23 protein expression in metastatic and non-metastatic tongue squamous cell carcinoma

O carcinoma de células escamosas oral (CCEO) exibe prognóstico desfavorável em decorrência da capacidade de invasão aos tecidos vizinhos e elevada incidência de metástases. OBJETIVO: O presente trabalho objetiva analisar a expressão imunohistoquímica da proteína nm23 em CCEs de língua metastáticos e não-metastáticos. METODOLOGIA: A técnica da imunohistoquímica para a proteína nm23-h1 foi realizada em 35 casos de CCE de língua com metástase em 15 casos. Atribuiu-se escore 0, para ausência de marcação; 1, marcação focal e 2 para marcação difusa. RESULTADOS: Observou-se marcação focal para a proteína nm23 em 9 casos, difusa em 15, e ausência de marcação em 11 espécimes. O teste exato de Fischer foi aplicado, não havendo diferença estatisticamente significativa para positividade desta proteína nos casos metastáticos e não-metastáticos (p=0.365), apesar de que em 66.7 por cento dos casos com metástase não houve marcação. CONCLUSÕES: A presença da proteína nm23 não esteve relacionada de forma positiva aos casos de CCE de língua sem metástase. Dessa forma, vários outros fatores inerentes à célula neoplásica e ao hospedeiro podem estar relacionados aos mecanismos supressores do processo metastático nesta entidade.

Oral squamous cells carcinoma (OSCC) shows unfavorable prognosis due to its invasion potential around the neighboring tissues and the elevated incidence of metastasis. AIM: the present paper aims at analyzing the immunohistochemical expression of the nm23 protein in metastatic and non-metastatic SCCs of tongue. METHODS: the immuno-expression to the nm23-hl protein was diagnosed in 35 tongue SCC (15 of which exhibiting metastasis). Nm23-hl immuno-scores were assigned as follow: score 0 = absent, 1 = focal and 2 = diffuse expression. RESULTS: The Fisher's exact test was performed and there was no statistical difference between the nm23-hl immuno-scores and the tongue SCCs studied cases (p=0.365), although 66.7 percent of metastatic cases presented negative nm23-hl expression. CONCLUSIONS: Protein nm23 was not associated with a positiveness for tongue SCC without metastasis. Thus, several others factors inherent to host and malignancy can be associated with the mechanisms that suppress the metastatic process in this disease.

Clinicopathologic Characteristics and p53, c-erbB2, nm23 Protein Expression in Gastric Remnant Cancer / 대한암학회지

PURPOSE: The goal of this study was to evaluate the clinicopathologic characteristics and to investigate the expression of p53, c-erbB2, and nm23 protein in gastric remnant cancer. MATERIALS AND METHODS: We evaluated the clinicopathologic characteristics and expression of p53, c-erbB2, and nm23 protein in 37 cases gastric remnant cancer (GRC) that detected at least 5 years after initial surgery, and compare them with adenocarcinoma from intact stomach. Twenty-seven patients among the 37 patients of GRC and 271 patients of primary gastric cancer (PGC) were chosen for immunohistochemical staining against p53, c-erbB2, and nm23. RESULTS: The median age was 59 years, male was predominant and median time interval between operations were 15 years. GRC initially operated for benign disease were detected later after initial gastrectomy and had a tendency toward lymph node metastasis than those initially operated for malignant disease. Resection was performed in 31 patients (81.0%) in whom 28 patient (71.0%) with curative intent. The overall 5-year survival rate was 44.8%. Multivariate analysis had revealed that depth of invasion was the most significant prognostic factor. p53, c-erbB2, and nm23 protein expression rates of GRC were 44.4%, 14.8%, and 66.7%, respectively and those of PGC were 45.4%, 16.2%, and 85.1%, respectively. p53 protein was more frequently expressed in well differentiated, Laurens intestinal carcinoma in both GRC and PGC. p53 protein expression and depth of invasion had an inverse relationship only in GRC. c-erbB2 protein was more frequently expressed in well differentiated, Laurens intestinal carcinoma in PGC. nm23 protein expression was more frequently expressed in the group of positive lymph node metastasis in GRC. CONCLUSION: Early detection by periodic endoscopic follow-up and radical resection is a reasonable treatment policy for GRC. The results of p53, c-erbB2, and nm23 expression suggest that they might have somewhat different roles in the pathogenesis and progression in GRC and PGC, so further study may be of benefit hereafter.

The clinical significance and detection of p53、c-erbB-2、p21、nm23 oncoprotein expression with immunohistochemical method in gastric cancer tissue / 中国免疫学杂志

Objective:To evaluate p53,c erbB 2,p21 and nm23 oncoprotein expression in diagnosis and treatment of gastric cancer.Methods:The expression of p53,c erbB 2,p21 and nm23 oncoproteins was detected with immunohistochemical method in 63 surgically resected specimens and its endoscopic biopsy specimens of gastric cancer.Results:The positive rates of p53,c erbB 2,p21 and nm23 oncoprotein expression were 37 6%～46 2%,34 6%～56 8%,37 8%～61 5%,70 3%～30 8% respectively.Oncoprotein expression was not observed in non tumor endoscopic biopsy specimens.The expression of c erbB 2,p21 was correlated with grade of tumor differentiation and the expression of p21,nm23 oncoproteins was correlated with the depth of tumor invasion and clinical different stage,namely tumor metastasis.Positive rates of p53,c erbB 2,p21 and nm23 oncoproteins between biopsy and resected specimens was of coincidence.Conclusion:Determination of p53,c erbB 2,p21 and nm23 oncoprotein expression was might be useful in diagnosis and treatment of gastric cancer,differentiating benign and malignant tumor and clinical stages,of gastric cancer. [

Nm23 Protein as a Prognostic Factor in Lymph Node Negative Breast Cancers

BACKGROUND: Nm23 gene was identified by the hybridization between two murine melanoma cell lines which had low or high metastatic potential and was located in chromosome 17q22. A number of tumor cohort studies have shown an inverse relationship between the levels of expression of nm23 protein and disease aggressiveness and tumor metastatic potential. METHODS: In order to determine the significance of overexpression of the antimetastatic gene nm23 protein in human-lymph node-negative breast cancer and to compare it with established clinicopathologic prognostic factors such as the tumor size, histologic grades, TNM stages, and hormonal receptor status, we analyzed the nm23 protein expressions by immunohistochemical staining in 53 lymph-node-negative breast-cancer tissue specimens. RESULTS: The nm23 protein expression was positive in 35 cases (66%). There was no relationship between nm23 protein overexpression and menopause status, tumor size, histologic grade, and hormonal receptor status, but tumor stage correlated with nm23 protein overexpression. Also, overexpression of the nm23 protein was significantly correlated with a longer disease-free survival rate. CONCLUSION: Expression of nm23 protein may be of value for predicting the long-term disease-free survival rate in lymph-node-negative breast-cancer patients.

The clinical relevance of nm23 protein expression in resected gastric cancer patient / 영남의대학술지

The aim of present study was to elucidate whether the expression of nm23 protein might be of clinical value as prognostic factor in gastric cancer. The expression of nm23 protein was analyzed using immunohistochemical method in formalin-fixed and paraffin-embedded tissue samples of 76 gastric carcinoma patients. The cytoplasmic immunoreactivity of nm23 protein were detected in 53.9%(41/76). When the immunoreactivity of nm23 protein with TNM status and other histopathologic findings were compared by using Chi-Square test, nm23 was found to have correlations with the lymph node metastasis(p=0.04), the number of metastatic lymph node, and the invasion of lymphatic vessels(p=0.007). But, it has no correlation with TNM status. The conventional prognostic factors such as the depth of invasion, lymph node metastasis, distant metastasis, Borrmann type, size of tumor, and the curability of operation was found to have strong correlation with the survival time(p<0.003). But, the expression of nm23 protein was not significantly correlated with that in survival analysis. These results showed that the expression of nm23 protein is not a useful prognostic indicator in gastric cancer.

Evaluation of Clinicopathologic and Prognostic Significance of nm23 protein in stage III Gastric Adenocarcinoma / 대한내과학회지

OBJECTIVE: Gene expression of nm23 has been investigated in a number of tumors, including breast cancer, colon cancer, malignant melanoma, and hepatocellular carcinoma. Its down-regulation has been shown to be associated with metastasis or disease progression in some of the tumors. This study was carried out to define the relationship between nm23 protein expression and clinicopathological variables. METHODS: nm23 protein levels were investigated in 64 surgically resected specimens of stage III gastric cancer by immunohistochemical method, and association with clinicopathological parameters and survival rates were determined. RESULTS: The overall expression rates of nm23 was 68.7 %. There was no significant difference between nm23 protein expression and clinicopathological variables such as age, sex, stage, histology, tumor depth, number of metastatic nodes, tumor size, site and method of operation. Statistically, no significant differences between nm23 protein expression and overall survival rates were found. CONCLUSIONS: These results suggest that nm23 protein expression is an unsatisfactory prognostic indicator in stage III gastric adenocarcinoma.

Expression of Urokinase-type Plasminogen Activator(uRA), Plasminogen Activator Inhibitor-1(PAI-1) and nm23 protein, as Prognostic Factors in Epithelial Ovarian Cancer / 대한부인종양콜포스코피학회잡지

The prognosis of ovarian cancer remains poor, and there is a need to identifiy patients who are less likely to respond to treatment, in the hope that the identification of these patients with a poorer prognosis may allow the administration of more intensive or different treatment. But, most clinical and pathological factors were considered to lack satisfactory predictive power. Recently, essential role of protease in tumor cell invasion and metastasis have been elucidated in tumor biology. Urokinase-type plasminogen activator (uPA) and its inhibitor, plasminogen activator inhibitor-1 (PAI-1), play a key role in tumor-associated proteolysis. Thus, the presence of both uPA and PAI-1 modulates the invasive and metastatic phenotype of cancer cells. Genetically, nm23 protein from chromosome 17q may act independently as a metastasis suppressor. The purpose of this study was to determine the relative predictive power of some of those prognostic variables such as uPA, PAI-1 and nm23 protein in a selected group of patients of ovarian cancer. Immunohistochemical staining was used to determine the overexpression of uPA, PAI-1 and nm23 protein. Specimens were rated positive and negative. Then, scored '1' in case of positive for uPA, PAI-1, and negative for nm23, and '0' in case of negative for uPA, PAI-1, and positive for nm23, respectively. The sum of scores were divided into three groups (I, II and III groups), and compared with clinico-pathologic parameters, clinical response, lymph node metastasis, recurrence and 5-year survival rate, retrospectively. In univariate analysis, the positive rate of uPA was 36% (29/80), that of PAI-1 was 35% (28/80), and the negative rate of nm23 was 43% (34/80). The overexpression of uPA was higher in the low-grade tumor (p=0.0053), the overexpression of PAI-1 was positively correlated with the advanced stage of tumor (p=0.0001), more malignant histologic type (serous) of tumor (p=0.0013) and larger residual tumor mass (>2 cm)(p=0.0480). The overexpression of nm23 protein was negatively correlated with advanced stage of tumor (p=0.0068) and low-grade tumor (p=0.011). In scoring system, the number of patients with first group (I: score 0) was 24, II group (score: 1~2) was 49, and III group (score: 3) was 7. The mean age of patients was 46.4 years and mean follow-up time was 59 months. The rate of lymph node metastasis were 16.7%, 37%, and 75% respectively(p=0.0632). With increasing score in each group, the less clinical response rate was found (75% vs 71% vs 29%, p=0.0532). The 5-year survival rate of each group were 70% in I group, 65% in II group, and 14% in III group(p=0.0096). In conclusion, the scoring system using immunohistochemical staining with rating of overexpression uPA, PAI-1 and nm23 protein may be useful as an important and powerful predictive prognostic indicator in patients with epithelial ovarian cancer.

Expression of Urokinase-type Plasminogen Activator(uRA), Plasminogen Activator Inhibitor-1(PAI-1) and nm23 protein, as Prognostic Factors in Epithelial Ovarian Cancer / 대한부인종양콜포스코피학회잡지

The prognosis of ovarian cancer remains poor, and there is a need to identifiy patients who are less likely to respond to treatment, in the hope that the identification of these patients with a poorer prognosis may allow the administration of more intensive or different treatment. But, most clinical and pathological factors were considered to lack satisfactory predictive power. Recently, essential role of protease in tumor cell invasion and metastasis have been elucidated in tumor biology. Urokinase-type plasminogen activator (uPA) and its inhibitor, plasminogen activator inhibitor-1 (PAI-1), play a key role in tumor-associated proteolysis. Thus, the presence of both uPA and PAI-1 modulates the invasive and metastatic phenotype of cancer cells. Genetically, nm23 protein from chromosome 17q may act independently as a metastasis suppressor. The purpose of this study was to determine the relative predictive power of some of those prognostic variables such as uPA, PAI-1 and nm23 protein in a selected group of patients of ovarian cancer. Immunohistochemical staining was used to determine the overexpression of uPA, PAI-1 and nm23 protein. Specimens were rated positive and negative. Then, scored '1' in case of positive for uPA, PAI-1, and negative for nm23, and '0' in case of negative for uPA, PAI-1, and positive for nm23, respectively. The sum of scores were divided into three groups (I, II and III groups), and compared with clinico-pathologic parameters, clinical response, lymph node metastasis, recurrence and 5-year survival rate, retrospectively. In univariate analysis, the positive rate of uPA was 36% (29/80), that of PAI-1 was 35% (28/80), and the negative rate of nm23 was 43% (34/80). The overexpression of uPA was higher in the low-grade tumor (p=0.0053), the overexpression of PAI-1 was positively correlated with the advanced stage of tumor (p=0.0001), more malignant histologic type (serous) of tumor (p=0.0013) and larger residual tumor mass (>2 cm)(p=0.0480). The overexpression of nm23 protein was negatively correlated with advanced stage of tumor (p=0.0068) and low-grade tumor (p=0.011). In scoring system, the number of patients with first group (I: score 0) was 24, II group (score: 1~2) was 49, and III group (score: 3) was 7. The mean age of patients was 46.4 years and mean follow-up time was 59 months. The rate of lymph node metastasis were 16.7%, 37%, and 75% respectively(p=0.0632). With increasing score in each group, the less clinical response rate was found (75% vs 71% vs 29%, p=0.0532). The 5-year survival rate of each group were 70% in I group, 65% in II group, and 14% in III group(p=0.0096). In conclusion, the scoring system using immunohistochemical staining with rating of overexpression uPA, PAI-1 and nm23 protein may be useful as an important and powerful predictive prognostic indicator in patients with epithelial ovarian cancer.

Expression of CD44 Splice Variants(v4/5 and v6), alpha-Smooth Muscle Actin, and nm23 Proteins in IB-IIB Uterine Cervical Cancer

We examined the expressions of CD44 splice variants (v4/5, v6), alpha-smooth muscle actin, nm23 to evaluate their roles as prognostic factors in 70 cases of uterine cervical carcinoma (stage IB to IIB) who were surgically treated from January 1989 to June 1990 with a clinical follow-up of a minimum of 5 years. The expression was examined by an immunohistochemical method using archival formalin fixed paraffin embedded tissue. In the 70 cases, 61 cases were squamous cell carcinoma and 9 cases were adenocarcinoma. CD44v4/5, CD44v6, alpha-smooth muscle actin, and nm23 were detected in 41.4%, 70%, 100%, and 74.3% of tumor samples, respectively. CD44 splice variants and nm23 showed membrane and cytoplasmic staining of tumor cells, respectively. The expression of alpha-smooth muscle actin showed cytoplasmic staining confined to stromal cells and was classified into three grades by the extent in stromal cells: with less than 10% of stromal cells; 32.9%, 10-50% of stromal cells; 40.0%, more than 50%; 27.1%. These expressions were not correlated with histologic types, lymph node involvement, recurrence, and grades of tumor infiltrating lymphocyte (TIL). But CD44v4/5 had significantly inverse correlation with TIL (p=0.049). The expression of CD44v4/5 was significantly correlated with that of CD44v6 (p=0.05), and that of alpha-smooth muscle actin was inversely correlated with that of nm23 (p=0.049). In conclusion, in FIGO IB-IIB uterine cervical carcinoma CD44 variants, nm23, and SMA show high prevalence, however, with little prognostic significance assessed by recurrence and lymph node metastasis.

Prognostic Value of nm23 Protein Expression and Tumor Angiogenesis in Breast Cancer

Mortality associated with human breast carcinoma is almost entirely due to subsequent cancer metastasis, but the molecular basis of this metastasis is not well established. The nm23 gene was originally identified by differential hybridization between two murine melanoma cell sublines which have low and high metastatic potential, and located in chromosome 17q22. This gene has been known to be involved in the metastasis of several cancers and its down-regulation usually associated with metastasis or disease progression in breast cancer. Tumor angiogenesis, the process leading to the formation of new vessels, plays a central role in tumor progression and distant metastasis. It is implicated in the phenomenon of dormant micrometastasis. This study was designed to determine the prognostic value of expression of the nm23 protein and tumor angiogenesis in breast cancer. Also, these two factors were compared with established clinicopathological prognostic factors and hormone receptors. 118 paraffin embedded surgical specimens of breast cancer were obtained from March, 1988 to February, 1994 and were selected for study. The expression of nm23 protein was studied by using immunohistochemical staining with anti-nm23/nuclear diphosphate kinase A. Tumor angiogenesis was quantified under light microscope by counting of the tumor microvessels(MVC) which were highlighted with anti-CD31 antibodies. The patient were allocated into two groups by mean number of MVC, one group was less 42 and the other was over 42. All the patients were female. The nm23 protein expression was positive in 74(63%) cases and was negative in 44(37%) cases. There was a significant correlation between nm23 protein expression and histologic grade(p=0.023). Positive expression of nm23 protein was correlated with positive estrogen(p=0.031) and progesterone receptors(p=0.001). Also Positive expression of nm23 protein was correlated with longer disease free survival(p=0.0026) and overall survival(p=0.0048). The group of MVC42. But the MVC and established clinicopathological prognostic factors did not show any correlation, neither with hormone status. When the nm23 protein and angiogenesis were considered together, 50 cases of negative nm23 protein and MVC<42 showed the best survival in overall(p=0.0111) and disease free survival(p=0.0114) among the four groups of each combination. In conclusion, the expression of nm23 protein and tumor angiogenesis can be used as new prognostic factors in conjunction with established other prognostic factors.

The correlation of p53 and nm23 expression with invasiveness and metastasis in colorectal carcinoma / 中国免疫学杂志

Objective:To study the relationship between expression of p53,nm23 and invasion and metastasis in human colorectal carcinoma,and the correlation between expression of p53 and nm23.Methods:Expression of p53 and nm23 were studied with SABC immunohistochemical technique Results:The positive rate of p53 and nm23 in 41 samples of human colorectal carcinoma was 58 5% and 53 7% respectively p53 over expression and nm23 low expression was significantly correlated with the depth of invasion and lymphatic metastasis The expression of p53 in pooly differentiated carcinoma was obviously higher than that in well differentiated carcinoma(P0 05) p53 over expression was correlated with nm23 low expression Conclusion:Over expression of p53 and low expression of nm23 might play an important role in invasion and metastasis of human colorectal carcinoma p53 over expression was related to the differentiation of colorectal carcinoma tissue