4项肿瘤标志物在肺癌诊断中的应用价值

目的探讨肿瘤标志物胃泌素释放肽前体(ProGRP)、神经元特异性烯醇化酶(NSE)、细胞角蛋白19的可溶性片段(CYFRA21-1)和鳞状细胞癌抗原(SCC)在肺癌诊断中的临床价值。方法选择151例肺癌及肺部良性病变患者为研究对象,其中小细胞肺癌(SCLC)43例,非小细胞肺癌(NSCLC)68例(包括腺癌35例、鳞癌33例),肺部良性病变患者40例,另选取健康体检者40例纳入健康对照组。采用罗氏电化学发光仪E601检测所有研究对象血清中的ProGRP、NSE、CYFRA21-1和SCC水平。结果 SCLC组的ProGRP和NSE水平均明显高于NSCLC-腺癌组、NSCLC-鳞癌组及肺部良性病变组,而NSCLC-腺癌组和NSCLC-鳞癌组的CYFRA21-1和SCC水平均明显高于SCLC组及肺部良性病变组,差异均有统计学意义(P<0.05)。在单项指标中,ProGRP在SCLC中的灵敏度和特异度最高,分别为77.2%和91.1%;CYFRA21-1在NSCLC-腺癌和NSCLC-鳞癌中的灵敏度和特异度较高,分别为65.9%和90.1%,以及71.5%和91.2%;在联合检测中,ProGRP+NSE在SCLC中的灵敏度和特异度分别为92.5%和83.6%;CYFRA21-1+SCC对NSCLC-腺癌和NSCLC-鳞癌的灵敏度在83.0%以上,特异度在85.0%以上。结论 ProGRP与NSE联合检测诊断SCLC的价值优于单项肿瘤标志物的检测;CYFRA21-1与SCC联合检测对NSCLC-腺癌和NSCLC-鳞癌有较高的灵敏度和特异度,这些肿瘤标志物诊断和筛查肺癌的潜力值得进一步研究。

Expression of Angiopoietin-2 and Vascular Endothelial Growth Factor in Oral Squamous Cell Carcinoma and Its Significance

Objective： To investigate the expression of angiopoietin-2 （Ang-2） and vascular endothelialcell growth factor （VEGF） in oral squamous cell carcinoma （OSCC） and their correlations with clinicopathologic parameters, angiogenesis and vessel maturation of OSCC. Methods： The expression of Ang-2 and VEGF was detected in 41 speciments of human OSCC, 30 adjacent noncancerous oral tissues and 10 specimens of normal oral mucosa by conventional immumohistochemistry. Microvessel density （MVD） and vessel maturation index （VMI） were also assessed by double-labelling immumohistochemistry staining against CD34, a marker of pan-endothelial cells, and that against alpha-smooth muscle actin （α-SMA）, a marker of mural cells （pericytes/smooth muscle cells）. Results： The positive expression rate of Ang-2 and VEGF in 41 OSCC tissues was 51.22% and 63.42%, respectively. The expression of Ang-2 and VEGF was significantly higher in OSCC than in adjacent noncancerous oral tissues （all P〈0.05） and normal oral mucosa （all P〈0.05）. In the clinicopathologic parameters, the Ang-2 expression was closely correlated with tumor lymph node metastasis （P〈0.01） and the VEGF expression was correlated with tumor differentiated degree （P〈0.05）, but there was no significant correlation among the Ang-2 and VEGF expression and patients＇ sex, age and TNM stages （all P〉0.05）. The MVD of OSCC positive for both Ang-2 and VEGF was significantly higher than that of OSCC negative for both Ang-2 and VEGF （P〈0.05）. The VMI of OSCC positive for Ang-2 was significantly lower than that of OSCC negative for Ang-2 （P〈0.05）. When Ang-2 expression was combined with the staus of VEGF expression, MVD of OSCC positive for both Ang-2 and VEGF was the highest （51.08±2.99） as compared with that of other status in patient with OSCC （all P〈0.05）. Conclusion： The overexpression of Ang-2 and VEGF may play a crucial role in the development of OSCC. They are closely associated with angiogenesis and vessel maturation of tumor.

THE EXPRESSION OF C－erbB－1 AND C－erbB－2ONCOGENES IN BASAL CELL CARCINOMA ANDSQUAMOUS CELL CARCINOMA OF SKIN

The expression of c-erbB-1 and c-erbB-2 oncogenes were investigated by immunohistochemistry using monoclonal antibodies to c-erbB-2 and c-erbB-2 protein in 43 cases of basal cell carcinoma (BCC) and 26 cases of squamous cell carcinoma (SCC). We found that the expression of c-erbB-1 oncogene in all BCC increased by different degrees and the expression of c-erbB-2 oncogene in BCC was significantly reduced or lost when compared to that in normal epidermal cells. Furthermore, apparent negative and positive rela-tionships were observed respectively between the tumor differentiation and the expression of cerbB-1 and c-erbB-2 oncogenes in SCC. It is suggested that the abnormal expression of c-erbB-1 and c-erbB-2 oncogenes in BCC and SCC may play a role in the development of skin tumors. The pattern of the c-erbB-1 and c-erbB-2 oncogenes expression in SCC may assist in distinguishing the biological behavior and prognosis of SCC.

Expression and clinical implication of p27 and p57 in cutaneous squamous cell carcinoma and Bowen's disease

Objective： To investigate the expression and clinical significance of cyclin dependent kinase inhibitors p27 and p57 in cutaneous squamous cell carcinoma and Bowen＇s disease. Methods： The expression of p27 and p57 were evaluated in 10 normal skin tissues, 25 Bowen＇s disease （BD） and 30 cutaneous squamous cell carcinoma （SCC） with immunohistochemistrical staining. Results： The levels of p27 protein expression in SCC were dramatically lower than those in normal skin and BD （P 〈 0.057. The levels of p57 protein expression in SCC were dramatically lower than those in normal skin and BD （P 〈 0.057. There was a posilk, e correlation between p27 and p57 （r = 0.469, P 〈 0.057. Conclusion： The decrease of p27 and skp2 may be used for considering the biological behavior of human cutaneous squamous cell carcinoma and Bowen＇s disease.

Effect of endothelin-1 in esophageal squamous cell carcinoma invasion and its correlation with cathepsin B

AIM： To investigate the effect of endothelin-1 in the invasion of esophageal cancer and determine whethel cathepsin B plays a role in the course. METHODS： Western blotting was employed tc detect the expression of ET-1 protein in 75 sample., of esophageal squamous cell cancer and matched normal esophageal rnucosa. Bosentan, a dual ET （A/B）- receptor antagonist, was used to inhibit the binding of endothelin-1 and its receptors and cut down its biological role. In vitro matrigel invasion assays were made to show the invasive ability of esophageal cancer cells with and without bosentan. Subsequently, we evaluated cathepsin B activity and expression in EC9706 cell with and without bosentan. RESULTS： We found 74.7% （56/75） tumors had an overexpression of ET-1 protein by Western blotting. Bosentan significantly inhibited matrigel invasion of cancer cells in vitro. EC9706 cells have a positive expression of cathepsin B protein, and bosentan can down-regulate its expression and activity. CONCLUSION： Endothelin-1 may enhance the invasive ability of human esophageal cancer cells, and its role is correlated with cathepsin B.

A Case Report of Thyroid Gland Squamous Carcinoma with Multiple Metastases

The patient was a female, 65 years to feel intermittent discomfort in old. Early in 1996, she began her neck, accompanied with hoarseness. In June, 2000, when she entered our hospital and accepted a physical examination, we found a 3 cm×2 cm tumor at the lower pole of the thyroid gland. Neck CT showed that the mass was located at the inferiorposterior right part of the thyroid gland with a diffuse boundary. MRI showed that the right thyroid cartilage wall was incomplete. Fine-needle aspiration cytology indicated a suspected papillary tumor.

Expression of Vascular Endothelial Growth Factor C and Its Clinical Significance in Human Esophageal Squamous Cell Carcinoma

OBJECTIVE To examine the expression of vascular endothelial growth factor C （VEGF-C） in human esophageal squamous cell carcinoma （ESCC）, and to clarify its role in lymphatic metastasis in ESCC patients.METHODS Esophageal carcinoma EC9706 cells and samples from 49 patients with primary ESCC were investigated by using S-P immunohistochemistry （IHC）, the semi-quantitative reverse transcriptase-polymerase chain reaction （RT-PCR） and in situ hybridization （ISH） methods for VEGF-C expression. RESULTS VEGF-C positive expression was found in EC9706 cells through IHC, ISH and RT-PCR. Positive IHC for VEGF-C was observed in 36 of 49 cases of ESCC. There was a significant difference between the expression of VEGF-C in a lymph-node-positive group compared to a node-negative group （χ^2=4.7, P〈0.05）. Positive ISH for VEGF-C mRNA was observed in 23 of 49 cases of ESCC. There was a significant difference between the expression of VEGF-C in the lymph-node-positive group and node-negative group （χ^2=31.3, P〈0.01）. The expression of VEGF-C was significantly higher in the lymph-node-positive group compared to the node-negative group. Of 49 ESCC tissues, RT-PCR for VEGF-C mRNA was observed positively in 29 cases. There was a significant difference between the expression of VEGF-C in the lymph-node-positive group and node-negative group （χ^2=23.3, P〈0.01）. The expression of VEGF-C was significantly higher in the lymphnode-positive group compared to the node-negative group. Expressions of VEGF-C were not significantly associated with age, gender, and pathological grade. There was a relationship between VEGF-C mRNA expressions by RT-PCR and ISH （χ^2=18.5, P〈0.01） in ESCC cases, but with no significant difference between the two methods. CONCLUSION VEGF-C expression may induce lymphangiogenesis in human ESCC. There was a close correlation between VEGF-C expression and lymph node metastasis. VEGF-C can serve as a useful prognostic factor for ESCC patients.

Prognostic Factors for Patients with FIGO Stage-IB Cervical Squamous Cell Carcinoma:Does the Tumor Size(≤4 cm or>4 cm)Really Matter?

OBJECTIVE To investigate the factors that can accurately predict the prognosis for patients with FIGO stage-IB cervical squamous cell carcinoma treated with radical surgery. METHODS A retrospective analysis of clinical data from 174 cases of FIGO Stage-IB cervical squamous cell carcinoma treated in our institute was conducted. RESULTS The 5-year overall disease-free survival of the patients was 79.4% and the recurrence rate was 16.7%. Seventy-five percent of the 60 patients with a tumor 〉 4 cm and 28.1% of the 114 patients with a tumor ≤ 4 cm received preoperative radiotherapy, resuting in a significant difference between the two groups （P 〈 0.001）. The 5-year disease-free survival rate for the groups with a tumor ≤ 4 cm without and with preoperative radiotherapy, and with a tumor 〉 4 cm without and with preoperative radiation therapy were 80.5%, 85.2%, 69.3% and 77.1%, respectively. There was no significant difference between any of the groups （P 〉 0.05）. A univariate analysis showed that pelvic node metastasis, a positive parametrial surgical margin and postoperative adjuvant therapy were all significantly correlated with the 5-year disease-free survivals （P 〈 0.05）. Multivariate analysis revealed that pelvic node metastasis （P = 0.004） and a positive parametrial surgical margin （P = 0.040） were independent factors that influenced the prognosis. The 5-year disease-free survivals for the cases with a tumor ≤ 4 cm and 〉 4 cm were 57.4% and 44.7% respectively in the high-risk group （patients with pelvic lymphatic metastasis and/or positive parametrial surgical margin） （P=0.575） and the recurrence ratio was 7/18 and 6/14 for the cases of the two tumor sizes in the same risk group. There was no significant difference between the two groups （P=0.821）. The 5-year disease-free survivals for the cases with a tumor ≤ 4 cm and 〉 4 cm were 86.5% and 82.9% respectively in the low-risk group （patients without pelvic lymph-node metastasis and/or positive parametrial surgical margin）, respectively （P 〉 0.05） and the recurrence ratio was 9/95 and 7/47 for the cases of the two tumor sizes in the same risk group. There was no significant difference between the two groups （P 〉 0.05）. CONCLUSIONS For FIGO Stage-IB cervical squamous cell carcinoma patients with radical surgery as the major means of treatment, the features of pelvic lymph-node metastasis and a positive parametrial surgical margin are independent factors that influence the prognosis. The tumor size can not be used as a criterion for predicting the prognosis.

Metastases of esophageal carcinoma to skeletal muscle:Single center experience

Metastases of esophageal carcinoma to the skeletal muscle are rare,but the incidence may be increasing because of better diagnosis resulting from widespread use of positron emission tomography/computed tomography(PET/CT).A cohort of 205 patients with esophageal carcinoma treated at our center who had PET/CT between 2006 and 2010 was retrospectively evaluated for the presence of skeletal muscle metastases.Four patients had skeletal muscle metastases of esophageal carcinoma,including two patients with squamous cell carcinoma.In another patient with squamous cell carcinoma of the esophagus and synchronous skeletal muscle metastases,muscle metastases were subsequently shown to be related to second primary pancreatic adenocarcinoma.In all cases,skeletal muscle metastases were the first manifestation of systemic disease.In three patients palliation was obtained with the combination of external beam radiation therapy,systemic chemotherapy or surgical resection.Skeletal muscle metastases are a rare complication of esophageal carcinoma.

The expression of HIF-1α and VEGF as well as their correlation with angiogenesis in esophageal squamous cell carcinomas

Objective： To investigate the correlations among the expressions of hypoxia-inducible factor-1α （HIF-1α）, vascular endothelial cell growth factor （VEGF） and microvessel density （MVD）, and their relationships to the clinicopathologic characteristics of esophageal squamous cell carcinomas （ESCC）. Methods： The expressions of HIF-1α, VEGF and MVD were detected by immunohistochemical method in 45 cases of ESCC, 30 intraepithelial neoplasia and 35 normal esophageal mucosal epithelia tissues. The correlations among the expressions of HIF-1α, VEGF and MVD, and their relationships to the clinicopathologic features of ESCC were analyzed. Results： The rate of positive expression of HIF-1α and VEGF which were 80% and 84% in ESCC were significantly higher than those in intraepithelial neoplasia and normal esophageal mucosal epithelium tissues （P 〈 0.01） and so did the MVD value which was71.10 ±15.02 in ESCC （P 〈 0.01）. The expression of HIF-1α and VEGF were positively correlated with the depth of tumor invasion, lymph node metastasis and TNM staging of ESCC. The expressions of HIF-1α were positively correlated with the expressions of VEGF and the value of MVD. Conclusion： Overexpression of HIF-1α is found in ESCC. HIF-1α may induce the angiogenesis in ESCC by upregulating the transcription of VEGF gene. It may play an important role in the carcinogenesis and aggression in ESCC, HIF-1α, VEGF and MVD may be a useful marker for evaluating the biological behaviors of ESCC.

A preliminary study on K-ras,EGFR,and B-raf mutations of esophageal squamous cell carcinoma

Objective: Molecular targeted drugs have been widely used in clinical application which has successfully prolonged some patients' life. Meanwhile, molecular targeted drug therapy for esophageal cancer are attracting more and more attention from doctors and experts. However, little study has been done towards the effect of this approach for treating esophageal squamous cell carcinoma. This paper, therefore, intends to explore the possibilities of applying EGFR-TKI inhibitors or anti-EGFR monoclonal antibody in esophageal squamous cell carcinoma by studying the mutations of EGFR, K-ras and B-raf in the esophageal squamous cell carcinoma tissues. Methods: Thirty-five cases of resected specimens of diagnosed esophageal squamous cell carcinoma with complete clinical and pathological data from January to April 2009 were collected. Pyrophosphate was used for observing the mutations of EGFR, K-ras and B-raf in the esophageal squamous cell carcinoma tissues. Results: Examinations were undertaken respectively to the codon segment 746-754 of exon 19 in EGFR genes, codon 12 and 13 in K-ras genes as well as condon 600 in B-raf genes. No mutation was found in EGFR and B-raf genes with mutation rate 0% (0/35), all of codon 12 in K-ras genes were wild-type without any mutation, while 2 specimens of codon 13 had mutations with mutation rate of 5.71% (2/35). Conclusion: In treating esophageal squamous cell carcinoma patients, all K-ras genes are expressed as wild type due to low mutation rate; cetuximab is effective due to low mutation rate of B-raf while EGFR-TKI inhibitor will not be effective enough because of low mutation rate of EGFR genes.