[Diagnosis and treatment of penile verrucous carcinoma: a report of 4 cases].

OBJECTIVE: To explore the diagnosis and treatment of penile verrucous carcinoma. METHODS: The clinical and pathological data of 4 patients with penile verrucous carcinoma were analyzed. RESULTS: The patients ranged in age from 42 to 76 years (average 52). All the tumors showed exophytic papillary lesions, the biggest being 2.1 to 5.8 cm in diameter. The lesions were confined to the glans penis in two cases and invaded the shafts in the other 2 (1 accompanied by syphilis). One patient, whose tumor was small (1.4 cm in diameter) and confined to the glans penis, underwent glandectomy. One with a larger tumor confined to the glans penis and the other 2 with the shafts involved underwent partial penectomy, including the one accompanied by syphilis, who underwent the operation after treated by Benzathine benzylpenicillin. Histopathological examination of the specimens showed that the tumor cells were mostly well-differentiated and the surgical margins were tumor free in all the 4 cases. HE stain was performed in all the specimens. Microscopic examination revealed papillomatosis and hyperkeratosis of the epithelium, with bulbous projections into the lamina propria consisting of well-differentiated squamous epithelial cells. Marked invasion of the stroma by lymphocytes was noted. Follow-up ranged from 3 to 7 years (average 4.6), revealing no recurrence. The result of the rapid plasma regain (RPR) test was negative but that of the Treponema pallidum passive-particle-agglutination (TPPA) test remained positive in the blood of the patient accompanied by syphilis after treatment. CONCLUSION: Verrucous carcinoma of the penis is characterized by low malignant potential and locally aggressive nature. It seldom develops metastasis to regional lymphonodes or distant areas. Glandectomy or partial penectomy can be chosen for its treatment, with favorable prognosis.

DNA ploidy analysis and expression of MMP-9, TIMP-2, and E-cadherin in gastric carcinoma.

AIM: To investigate DNA ploidy and expression of MMP-9, TIMP-2, and E-cadherin in gastric carcinoma and to explore the mechanism of invasion and metastasis of gastric carcinoma. METHODS: Immunohistochemical methods were used to detect the expressions of MMP-9, TIMP-2, and E-cadherin in 156 cases, including 99 cases of gastric carcinoma, 16 cases of adjacent noncancerous mucosa, 16 cases of distant metastases and 25 cases of metastatic lymph node (LN) from gastric carcinoma. Flow cytometry DNA ploidy and S-phase fraction (SPF) analysis were performed on 57 cases, including 47 cases of gastric cancer, 6 cases of adjacent noncancerous mucosa, and 4 cases of distant metastatic cancer. RESULTS: The expression of MMP-9 was significantly correlated with Lauren's classification, Borrmann's classification, LN metastasis, tumor metastasis, and TNM stage, as well as depth of invasion (all P<0.05). The positive rate was lower in noncarcinoma than in carcinoma (31.3% vs 66.7%, P<0.01). The expression of TIMP-2 was significantly correlated with Borrmann's classification, LN metastasis, and the depth of invasion (all P<0.05). The expression of E-cadherin was significantly correlated with differentiation, Lauren's classification, Borrmann's classification, and LN metastasis, as well as the depth of invasion (P<0.01 or P<0.05). E-cadherin was less expressed in carcinoma than in noncarcinoma (42.4% vs 87.5%, P<0.01). There was a positive correlation between MMP-9 and TIMP-2 and a negative correlation between MMP-9 and E-cadherin, but no correlation between TIMP-2 and E-cadherin. Also there was a positive correlation between DNA aneuploid rate and differentiation and LN metastasis. SPF that was higher than 15% was positively correlated with tumor size, differentiation and LN metastasis. And there was a significant difference between carcinoma and noncarcinoma in DNA aneuploid rate and SPF. CONCLUSION: With tumor progression and development of heterogeneity, the abnormal expressions of MMP-9, TIMP-2, and E-cadherin or DNA aneuploid rate or high SPF gradually increases, suggesting that they play a crucial role in gastric carcinoma progression.

Beta-catenin up-regulates the expression of cyclinD1, c-myc and MMP-7 in human pancreatic cancer: relationships with carcinogenesis and metastasis.

AIM: To investigate whether abnormal expression of beta-catenin in conjunction with overexpression of cyclinD1, c-myc and matrix metalloproteinase-7 (MMP-7) correlated with the carcinogenesis, metastasis and prognosis of pancreatic cancer, and to analyze the relationship of beta-catenin expression with cyclinD1, c-myc and MMP-7 expression. METHODS: Using immunohistochemistry, we examined the expression of beta-catenin, cyclinD1, c-myc and MMP-7 in 47 pancreatic adenocarcinoma tissues, 12 pancreatic intraepithelial neoplasia (PanIN) and 10 normal pancreases, respectively. Proliferation cell nuclear antigen was also tested as the index of proliferative activity of pancreatic cancer cells. RESULTS: In 10 cases of normal pancreatic tissues, epithelial cells showed equally strong membranous expression of beta-catenin protein at the cell-cell boundaries, but the expression of cyclinD1, c-myc and MMP-7 was negative. The expression of beta-catenin, cyclinD1, c-myc and MMP-7 in PanIN and pancreatic adenocarcinoma tissues had no significant difference [6/12 and 32/47 (68.1%), 6/12 and 35/47 (74.5%), 5/12 and 33/47 (70.2%), 7/12 and 30/47 (63.8%), respectively]. The abnormal expression of beta-catenin was significantly correlated to metastasis and one-year survival rate of pancreatic cancer, but had no relation with size, differentiation and cell proliferation. The expression of cyclinD1 was correlated with cell proliferation and extent of differentiation, but not with size, metastasis and one-year survival rate of the pancreatic cancer. The expression of c-myc was not correlated with size, extent of differentiation, metastasis and 1-year survival rate, but closely with cell proliferation of pancreatic cancer. The overexpression of MMP-7 was significantly associated with metastasis and 1-year survival rate of pancreatic cancer, but not with size, extent of differentiation and cell proliferation. There was a highly significant positive association between abnormal expression of beta-catenin and overexpression of cyclinD1, c-myc and MMP-7 not only in PanIN (r = 1.000, 0.845, 0.845), but also in pancreatic cancer (r = 0.437, 0.452, 0.435). CONCLUSION: The abnormal expression of beta-catenin plays a key role in the carcinogenesis and progression of human pancreatic carcinoma by up-regulating the expression of cyclinD1, c-myc and MMP-7, resulting in the degradation of extracellular matrix and uncontrolled cell proliferation and differentiation. beta-catenin abnormal expression and MMP-7 overexpression may be considered as two useful markers for determining metastasis and prognosis of human pancreatic cancer.

[A study of the relationship between the expression of connexin43, E-cadherin and biological behaviors of human laryngeal cancer].

OBJECTIVE: To investigate expression of connexin43 (Cx43) and E-cadherin (E-cad) and its relationship with the biological behavior in Laryngeal carcinomas. METHODS: Immunohistochemistry staining (PicTure two steps method) was used to detect connexin 43 and E-cadherin expression in 60 paraffin-embedded laryngeal carcinomas and 10 normal epithelia around tumors. All the patients were followed up more than five years. RESULTS: Cx43 and E-cad were expressed by normal epithelia with typical membranous staining 10 normal epithelia strongly expressed Cx43 and E-cad. The reduction rate of Cx43 expression in laryngeal carcinomas was 30.0%. The significant relationship was observed between low Cx43 expression and differentiation, lymph node metastasis and recurrence (chi2 = 15.09, 6.41, 3.86, P < 0.01, 0.05, 0.05), but there was no significance between low Cx43 expression and prognosis (chi2 = 2.65, P > 0.05). 41.7% laryngeal carcinoma showed reduced or no expression of E-cad. Tumor cell dedifferentiation correlated with reduced expression for E-cad (chi2 = 15.07, P < 0.01). Absent or low E-cad expression was observed more frequently in patients with local recurrence and lymph node metastasis and with less than 5-year survival period (chi2 = 5.35, 6.65, 5.14; P < 0.05, 0.01, 0.05). There was a positive relationship between the expression of Cx43 and E-cad in same sample (r = 0.63, P < 0.0001). CONCLUSIONS: Laryngeal cancer presented inactivation of Cx43 gene and E-cad gene and down regulation of Cx43 and E-cad proteins. The level of Cx43 and E-cad may be a sensitive predictor of differentiation, invasion, lymph node metastasis and recurrence. E-cad is also a prognostic factor for patients with laryngeal cancer.

Relationship between expressions of E-cadherin and alpha-catenin and biological behaviors of human pancreatic cancer.

OBJECTIVES: To investigate the expressions of E-cadherin and alpha-catenin in pancreatic carcinoma and their relationship with biological behaviors, and clarify the mechanism of invasion and metastasis of pancreatic cancer. METHODS: The expressions of E-cadherin and alpha-catenin was examined in 47 patients with infiltrative ductal adenocarcinoma of the pancreas and 12 specimens of normal pancreatic tissues by immunohistochemical technique (PicTure( trade mark ) two-step method). Proliferation cell nuclear antigen (PCNA) was tested as an index of the proliferation degree of pancreatic cancer cells. RESULTS: The immunoreactivity of E-cadherin and alpha-catenin was expressed by normal ductal and acinar cells with strong membranous staining at the intercellular border in 12 specimens of normal pancreatic tissues. The abnormal rate of E-cadherin expression in pancreatic cancer was 53.2% (25/47), and it was significantly related to differentiation, high proliferation degree and lymph node and liver metastases (P<0.01, 0.05, 0.05 and 0.01, respectively). 61.7% patients with pancreatic cancer (29/47) showed abnormal expression of alpha-catenin. There was a good correlation among alpha-catenin expression, histological grade, and lymph node and liver metastases (P<0.05,0.05 and 0.01, respectively). No significant association was found among abnormal expressions of E-cadherin and alpha-catenin, tumor size, invasion, and 1-year survival rate of patients (P>0.05, all). There was a positive relationship between the expressions of E-cadherin and alpha-catenin in the 47 patients with pancreatic cancer (P<0.01, r=0.88). CONCLUSIONS: Pancreatic cancer likely occurs in case of the inactivation of E-cadherin and alpha-catenin genes and abnormal expression of proteins, which significantly correlate with tumorigenesis, proliferation, differentiation, and lymph node or liver metastasis of pancreatic cancer.

[Relationship between the expression of beta-cat, cyclin D1 and c-myc and the occurance and biological behavior of pancreatic cancer].

OBJECTIVE: To study the relationship between the abnormal expression of beta-catenin (beta-cat) and the high expressions of cyclin D1 and c-myc and the occurance, proliferation, infiltration, metastasis and prognosis of pancreatic cancer, and to provide rational basis for the clinical diagnosis and treatment. METHODS: Immunohistochemical PicTure trade mark was used to examine the expressions of beta-cat, cyclin D1 and c-myc in 47 cases of the cancerous tissue of pancreas, 12 cases of the pancreatic intraepithelial neoplasia and 10 cases of normal tissue of pancreas, respectively. Pancreatic cancer proliferation cell nuclear antigen (PCNA) was also tested as the index of the extent of proliferation of the pancreatic cancer. RESULTS: beta-cat was expressed normally in the 10 cases of the normal pancreatic tissue, while cyclin D1 and c-myc were negative. The expression rates of beta-cat, cyclin D1 and c-myc in the tissues of the pancreatic intraepithelial neoplasia and the pancreatic cancer had no significant difference [6/12 and 68.1% (32/47), 6/12 and 74.5% (35/47), 5/12 and 70.2% (33/47) respectively;P values were all more than 0.05]. The abnormal expression rate of beta-cat was significantly correlated to the metastasis of the pancreatic cancer and the one-year survival rate (both P < 0.05), but had no relation with the size, the extent of differentiation, the activity of proliferation, or infiltration of the pancreatic cancer (both P > 0.05). The expression rate of cyclin D1 was correlated with the proliferation of the pancreatic cancer and the extent of differentiation (both P < 0.05), but not with the size, infiltration, metastasis, or one-year survival rate of the pancreatic cancer (both P > 0.05). The expression rate of c-myc was not correlated with the size, the extent of proliferation, infiltration, metastasis, or one-year survival rate (both P > 0.05), but closely with the proliferation activity of the cancerous tissue of pancreas (P < 0.05). The abnormal expression of beta-cat and the high expressions of cyclin D1 and c-myc had a parallel relationship with the pancreatic intraepithelial neoplasia and pancreatic cancer (both P < 0.05, gamma = 1.000, 0.845, 0.437, 0.452). CONCLUSIONS: The abnormal expression of beta-cat activates cyclin D1 and c-myc, and results in the unchecked proliferation and differentiation, which may play an important role in the genesis of the pancreatic cancer. The abnormal expression of beta-cat is one of the mechanisms for the spread of pancreatic cancer and an index in the molecular biology to determine the metastasis and prognosis of pancreatic cancer.

Relationship between expression of E-cadherin-catenin complex and clinicopathologic characteristics of pancreatic cancer.

AIM: To investigate the expression of E-cadherin and alpha-catenin and beta-catenin in pancreatic carcinoma and its relationship with the clinicopathologic characteristics, and clarify the mechanism of invasion and metastasis of pancreatic cancer. METHODS: The expression of E-cadherin and alpha-, beta-catenin was examined in 47 cases of infiltrative ductal adenocarcinoma of pancreas and 12 adult normal pancreatic tissues by immunohistochemical technique. RESULTS: The immunoreactivity of E-cadherin and alpha-, beta-catenin was expressed by normal ductal and acinar cells with strong membranous staining at the intercellular border in 12 cases of adult normal pancreatic tissues. Abnormal expression of E-cadherin and alpha-, beta-catenin in 47 pancreatic carcinoma tissues was demonstrated in 53.2 %, 61.7 % and 68.1 %, respectively. Both abnormal expression of E-cadherin and alpha-catenin significantly correlated with differentiation, lymph node and liver metastases (P<0.05, respectively), whereas aberrant beta-catenin expression only correlated with lymph node and liver metastases (P<0.001). Abnormal E-cadherin and alpha-, beta-catenin expression was not associated with tumor size, invasion and survival time of patients (P>0.05, all). CONCLUSION: Pancreatic cancer likely occurs in case of E-cadherin-catenin complex genes mutations or deletions and abnormal expression of proteins, which significantly correlate with the biologic character of the tumor and lymph node and liver metastases. It is suggested that the abnormal E-cadherin-catenin complex expression plays an important role in the development and progression of tumor, and thus may become a new marker in pancreatic cancer metastasis.

[Expression of CGRP, ACTH and 5-HT in normal human lymph nodes].

AIM: To detect the expression of calcitonin-gene-related peptide (CGRP), adrenocorticotropin (ACTH), and serotonin (5-HT) in normal human lymph nodes and explore their influences on immune system. METHODS: The expression of CGRP, ACTH and 5-HT in the lymph nodes, including proliferative lymph nodes, were detected by SABC Immunohistochemical staining. RESULTS: In 35 cases of lymph node specimens, the positive rates of CGRP, ACTH and 5-HT expression were 88.5%(31/35), 85.4%(30/35) and 94.2%(33/35) respectively. These 3 molecules had a similar distribution in germinal center of lymph nodes, mainly in the cells of paracortical region, the cells in germinal center of lymph follicles and macrophages, etc. CONCLUSION: There are considerably high positive rates of CGRP, ACTH and 5-HT in human peripheral lymph nodes, and their distribution area are basically coincident with that of immunocytes in the lymph nodes.