Influence of lymph vascular space invasion on prognosis of patients with early-stage cervical squamous cell carcinoma / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>In the past decade, no remarkable improvement has been made in the 5-year survival of cervical cancer patients. This study was to explore the influence of lymph vascular space invasion (LVSI) on the prognosis of patients with early-stage cervical squamous cell carcinoma.</p><p><b>METHODS</b>A total of 111 eligible patients with FIGO stage IB and IIA cervical squamous cell carcinoma underwent radical hysterectomy and pelvic lymphadenectomy at Sun Yat-sen University Cancer Center between January 1995 and December 2002. The histopathological slides of the 111 patients were reviewed by a senior gynecological pathologist. LVSI, invasion depth, tumor differentiation and lymph node metastasis were evaluated.</p><p><b>RESULTS</b>LVSI was present in 62 patients. The univariate analysis showed that the risk factors of overall survival (OS) included positive LVSI (P = 0.019) and lymph node metastasis (P = 0.002), while the risk factors of progression-free survival (PFS) included LVSI (P = 0.029), lymph node metastasis (P = 0.002), SccAg value (P = 0.018), invasion depth (P = 0.022) and positive surgical margin (P = 0.002). The multivariate analysis showed that lymph node metastasis was the independent prognostic factor of OS (P = 0.015), while lymph node metastasis and positive surgical margin were the independent factors of PFS (P = 0.006, P = 0.006). LVSI was correlated with lymph node metastasis (P = 0.011).</p><p><b>CONCLUSION</b>Whether LVSI is an independent prognostic factor of early-stage cervical squamous cell carcinoma cannot be determined currently while LVSI is a risk factor of metastasis and relapse.</p>

Expressions of epidermal growth factor receptor in primary nasopharygeal carcinoma and lymph node metastases / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the expressions of epidermal growth factor receptor (EGFR) in primary nasopharygeal carcinoma (NPC) and lymph node metastases.</p><p><b>METHODS</b>Archived samples of primary NPC and paired lymph node metastases from 86 patients were examined immunohistochemically for the protein expression of EGFR.</p><p><b>RESULTS</b>EGFR expression positivity was detected in the primary NPC and lymph node metastases at the rate of 73.3% and 60.5%, respectively, and primary and metastatic foci showed significant difference in the expression levels (P=0.001). A discrepancy of EGFR expression between the primary and metastatic foci was found in 25 patients, with a discrepancy rate of 29.1% (25/86).</p><p><b>CONCLUSION</b>The difference in EGFR expression between the primary and lymph node metastastic foci of NPC needs to be evaluated when performing EGFR-targeted therapies especially in advanced NPC cases.</p>

Impact of visceral pleural invasion on the prognosis of stage Ib non-small cell lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the impact of visceral pleural invasion (VPI) on prognosis and staging in patients with stage Ib non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>Clinical data of 232 patients with stage Ib NSCLC surgically treated by curative resection between January 1994 and December 2003 was retrospectively reviewed. Histopathological diagnosis was reviewed by an experienced pathologist. According to the tumor size and status of VPI, patients were stratified into three group: group A: tumor > 3 cm and VPI(-); group B: tumor < or = 3 cm and VPI (+); group C: tumor > 3 cm and VPI(+). There were 45 patients in group A, 96 in group B and 91 in group C. Kaplan-Meier method was used for survival analysis. Cox proportional hazards model was used for multivariate analysis.</p><p><b>RESULTS</b>187 (80.6%) patients had visceral plural invasion, while 45 (19.4%) had no. The 5-and 10-year survival rates of patients with VPI were 59.3% and 42.6%, while it was 70.1% and 56.7% for the patients without (P = 0.035), respectively. The 5-year survival rates of patients in group A, B and C were 70.1%, 61.9% and 56.2%; and 10-years survival rates were 56.7%, 50.6% and 35.9%, respectively (P = 0.018). VPI with large size of tumor was revealed by Cox multivariate analysis as an independent prognostic factor (RR = 1.530, 95% CI: 1.132-2.067, P = 0.006).</p><p><b>CONCLUSION</b>A significant difference in survival exists among the stage Ib NSCLC patients who have different T status, the patient with > 3 cm tumor and visceral plural invasion may have the worst prognosis. Further studies are still needed to assess whether it is necessary or not to modify the T2 statue of tumor > 3 cm with visceral plural invasion.</p>

Effects of MT1-MMP on the in vitro invasiveness of breast cancer cells / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the effect of membrane type-1 matrix metalloproteinase (MTI-MMP) on the invasive potential of breast cancer cell and analyze its mechanisms.</p><p><b>METHODS</b>After treatment of breast cancer MDA-MB-453 cell line with concanavalin A ( ConA, 20 microg/ml) for 24 h, MT1-MMP protein was detected in cancer cells by Western analysis and immunocytochemistry. MDA-MB-453 cells were cultured with exogenous latent proMMP-2 and MMP-2 activity was analyzed by gelatin zymography. The invasive potential of the tumor cells was measured with a membrane invasion culture system. Cancer cells of the cell line were divided into four groups: the control group treated by neither reagent, group ConA was only treated by ConA, group MMP-2 was treated only by MMP-2, and group ConA + MMP-2 was treated by both ConA and MMP-2. RESULTS The expression of MTI-MMP protein could be detected in groups ConA and ConA + MMP-2, but nothing was detected in control and group MMP-2. There was only 72 000 precursor form of MMP-2 in group MMP-2 and there were both 72 000 precursor form and 64 000 active enzyme form of MMP-2 in group ConA + MMP-2, but there was no forms of MMP-2 in the other two groups detected by gelatin zymography. The largest amount of cells penetrated through Matrigel was observed in group ConA + MMP-2 than in the other three groups.</p><p><b>CONCLUSION</b>MTI-MMP can remarkably promote the invasive potential of breast cancer cells mainly through its ability of activating latent proMMP-2 to degrade</p>

Effects of citrus reticulata blanco extract on fibroblasts from human hypertrophic scar in vitro / 中华烧伤杂志

<p><b>OBJECTIVE</b>To investigate the effects of citrus reticulata blanco extract on the proliferation and collagen metabolism of fibroblasts from human hypertrophic scar.</p><p><b>METHODS</b>Human hypertrophic scar fibroblasts from two burn patients obtained from plastic surgery were cultured in vitro and divided into experimental group (n = 12, with basic culture medium and 2.5, 5.0, 10.0,25.0 mg/L citrus reticulata blanco extract, respectively, 3 bottles for each concentration of citrus reticulata blanco extract ), control group 1 (n = 3, with basic culture medium) , and control group 2 ( n = 3, with basic culture medium and 5% ethyl alcohol). The cell proliferation in each group was observed with MTT method, then the inhibition rate was calculated. Apoptosis and its index ( AI) in each group were determined after TUNEL staining . The changes in the content of ICTP and PINP in each group were observed by radioimmunity.</p><p><b>RESULTS</b>The inhibition rate in the experimental group with the citrus reticulata blanco extract in concentration of 2. 5, 5.0, 10.0, 25. 0 microg/ ml were (7. 100+/-0.038)% , (8. 100+/- 0. 048)% , (10. 900+/-0. 055)%, (15.900+/-0. 097) %, respectively, which were significantly higher than those in other two groups ( P <0.05 ). The Al (69. 7% , 71.7%, 86.4% , 95.2% ), ICTP [(17.2+/-0.6), (18.3+/-0.6), (19.8+/-0.5), (23.2+/-0.6) microg/L] and PINP [ (101.7+/-1.4) , (107. 8+/-1. 1) , (111.6+/-1.2) , (124. 6+/-1.3) microg/L] in experimental group with the citrus reticulata blanco extract in concentration of 2.5, 5.0, 10.0 , 25.0 mg/L were also obviously higher than other two control groups( P <0.05) ,but these indices in control 1 group were similar to those in control 2 group( P >0. 05).</p><p><b>CONCLUSION</b>The citrus reticulata blanco extract might be beneficial for the management of hypertrophic scar through inhibition of the proliferation of fibroblasts in hypertrophic scar, by promoting apoptosis and collagen degradation.</p>

Expression of hepatocyte growth factor/c-Met system in nasopharyngeal carcinoma and its biological significance / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the expression of hepatocyte growth factor (HGF), and its receptor c-Met protein in nasopharyngeal carcinoma (NPC) and CNE-2 NPC cell line, to correlate their expression level with clinicopathologic features and to study the effect of HGF/c-Met system on the invasive and metastatic potential of NPC.</p><p><b>METHODS</b>Forty-five biopsies were collected from pre-treatment NPC patients during the period from 1999 to 2003. Immunohistochemical staining was used to detect the expression of HGF-alpha subunit and c-Met protein in NPC tissues. The association between expression of these proteins and clinicopathologic features was statistically analyzed. The expression of HGF and c-Met, as detected by flow cytometry, in CNE-2 NPC cell line (with or without exogenous HGF) was compared. Western blot analysis and reverse transcriptase-polymerase chain reaction (RT-PCR) were also applied to evaluate the protein and mRNA expression of c-Met in CNE-2 cells.</p><p><b>RESULTS</b>In the 45 cases studied, the expression rate of c-Met was 91.1% (41/45). Only 1 case (2.2%, 1/45) showed positive signal for HGF in neoplastic cells. Instead, HGF was expressed in surrounding lymphocytes. The expression of c-Met positively correlated with lymph node metastasis (P = 0.024). There was also a positive correlation between expression of c-Met by tumor cells and expression of HGF by surrounding lymphocytes (r(s) = 0.450, P = 0.002). Moreover, the expression of c-Met was higher if there was a higher expression of HGF by lymphocytes (P = 0.009). However, there was no association between expression of c-Met and clinicopathologic features, such as age, gender, histopathologic type and clinical stage. After treatment with HGF for 24 hours, the percentage of c-Met-positive cells was significantly increased in CNE-2 cell line, from (46.6 +/- 9.02)% to (85.8 +/- 6.05)% (P = 0.003). The c-Met protein expression and c-Met mRNA level were also enhanced in CNE-2 cells with HGF treatment. However, endogenous HGF was not detected in CNE-2 cells, regardless of HGF treatment.</p><p><b>CONCLUSIONS</b>HGF may play an important role in the development of NPC metastasis by inducing the expression of c-Met in tumor cells via a paracrine, instead of an autocrine, pathway.</p>

Primary adenoid cystic carcinoma of the nasopharynx and its relation to Epstein-Barr virus infection / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathologic characteristics of primary nasopharyngeal adenoid cystic carcinoma (NPACC) and its relation to Epstein-Barr virus (EBV) infection in Guangzhou where is a high-incidence area of EBV-associated nasopharyngeal carcinoma (NPC).</p><p><b>METHODS</b>17 cases of NPACC with clinical record and biopsy samples were collected in Guangzhou and their clinical manifestations were reviewed. Besides HE, Alcian blue and PAS, LSAB immunohistochemistry was performed for detecting the expression of a variety of epithelial markers, CD21 and EBV encoded LMP1. EBV encoded early RNAs (EBER) was detected by using in-situ hybridization. Nested PCR was applied for studying the presence of EBV W-fragment in tissues.</p><p><b>RESULTS</b>The ratio of male to female was 7:10. The patients' age ranged from 30 to 63 years, and the median age was 46 years. 14 out of 17 tumors showed markedly local aggressive growth, presenting as T3 or T4. However, only 1 patient had metastasis of an ipsilateral cervical lymph node. The majority of neoplastic cells were basal-cell like in shape and with scanty cytoplasm and a deeply stained nucleus. Intercellular hyaline or mucinous substance was always present in between the carcinoma cells. Cribriform structure formed by the neoplastic cells could be found in 16 out of these 17 biopsies. The NPACC always express the wide-spectrum cytokeratin and the epithelium membrane antigen. Only a few or a small number of carcinoma cells showed nuclear EBER-signals in 9 cases (9/17). Concurrently, these 9 NPACCs showed a 192 bp W-fragment positive band on electrophoresis gel by nested PCR. LMP1 expression had been found in 5 out of the 9 NPACCs (55.6%) accompanying with EBER-positive carcinoma cells. The EBER-positive infiltrating lymphocytes could also be found in the stroma of 3 out of the 9 EBER-stained NPACC slides. All the tumor cells, including the EBER-positive cell of the 17 NPACCs showed no CD21 expression.</p><p><b>CONCLUSIONS</b>The female is predominant over the male in development of NPACC, which often accompanied with a markedly invasive capacity at the nasopharynx and its neighboring sites. Only a small number of tumor cells, nearly a half of the studied cases were infected with EBV. Therefore, it's postulated that there seems no close relation present between NPACC and EBV infection.</p>

Comparison of the Epstein-Barr virus infection and 30 bp-deleted LMP1 gene among 4 histologic types of nasopharyngeal carcinoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To compare the Epstein-Barr virus (EBV) infection rates and the frequencies of wt-LMP1 and del-LMP1 EBV variants detected singly or dually among the four types of nasopharyngeal carcinoma (NPC) and to illustrate the possible role of del-LMP1 gene in nasopharyngeal carcinogenesis.</p><p><b>METHODS</b>EBER in situ hybridization was performed in 117 NPCs, including 48 non-keratinizing carcinomas (NKCs), 25 keratinizing squamous cell carcinomas (KSCCs), 5 adenosquamous carcinomas (ASCs), 6 mucoepidermoid carcinomas (MECs) and 33 adenocarcinomas (ACs). Nested PCR for demonstration of EBV LMP1 gene was performed on the tissue samples collected from 99 EBER-positive carcinoma cases and the peripheral blood mononuclear cells (PBMCs) of 53 healthy adults (HAs).</p><p><b>RESULTS</b>As indicated by EBER in-situ hybridization, the EBV infection rates in both of 48 NKCs and 25 KSCCs were 100%; and the infection rates of 11 ASCs/MECs and 33 ACs were 9/11 and 51.5% (17/33), respectively. Worthy to note was that most of the NKC cells were EBER-positive while only a small number of EBER-positive neoplastic cells could be found in 17 ACs. The percentage of del-LMP1 EBV variant detected singly in NKCs (85.4%, 41/48) was not only significantly higher than that in PBMCs of 46 HAs (8.7%, 4/46) but also significantly higher than those detected in KSCCs (16.0%, 4/25). The dual infection rate of wt-LMP1 and del-LMP1 variants detected in KSCCs (56.0%, 14/25) was significantly higher than that of NKCs (12.5%, 6/48). The majority of the EBV detected in AC tissues (12/17) and HAs' PBMCs (34/46, 73.7%) were of dual wt-LMP1 and del-LMP1 variants.</p><p><b>CONCLUSIONS</b>The EBV infection rates are significantly different among 3 major histological categories, namely, NKC/KSCC, ASC/MEC and AC. Though NKCs and KSCCs are always consistently associated with EBV, the single del-LMP1 EBV variant detected in NKCs is predominant over that in KSCCs and most of the KSCCs contain dual wt-LMP1 and del-LMP1 EBV variants. The EBV of the del-LMP1 variant might play a crucial role in carcinogenesis of NKC.</p>