Ji-You Li

Matrix Metalloproteinases Expression Correlates with Survival in Patients with Esophageal Squamous Cell Carcinoma

OBJECTIVES:The matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases capable of degrading the extracellular matrix and play important roles in malignancies. We evaluated the expression of four MMPs in esophageal squamous cell carcinoma (ESCC), and assessed the association between MMP expression and clinicopathologic characteristics and disease-free survival time.METHODS:We evaluated MMP1, MMP7, MMP9, and MMP13 expression in tissues from 208 patients with ESCC using immunohistochemistry (IHC), and correlated MMP expression to clinicopathologic characteristics and disease-free survival time. To confirm MMP9 expression at different levels, we simultaneously performed RT-PCR, Western blotting, and IHC on tissues from a separate cohort of 23 patients with ESCC.RESULTS:IHC analysis showed that 63.0%, 41.8%, 49.0%, and 32.2% of 208 ESCC samples were positive for MMP1, MMP7, MMP9, and MMP13, respectively. MMPs were strongly expressed in the cytoplasm of cancer cells, especially in the invasive margin, and weakly expressed in stromal cells. No immunostaining was detected in non-cancerous esophageal mucosa. MMP9 expression was positively associated with poor tumor cell differentiation (P = 0.001), vessel permeation (P = 0.027), and lymph node metastasis (P = 0.027). MMP9 expression was a negative, independent predictor of disease-free survival time (Hazard ratio, 1.470; 95% CI, 1.105 ∼ 1.955; P = 0.008). The expression of MMP7 (median survival time: 23 months for MMP7 positive patients, >77 months for MMP7 negative patients; P = 0.001) and MMP13 (median survival time: 18 months for MMP13 positive patients, 39 months for MMP13 negative patients; P = 0.014) correlated negatively with disease-free survival in relatively early stage ESCC patients. Co-expression of MMP7, MMP9, and MMP13 in relatively early stage ESCC samples identified patients with a poor prognosis (13 months median survival time) compared to those lacking MMP7, MMP9, and MMP13 expression (58 months median survival time, p < 0.001).CONCLUSIONS:MMP9 expression is a negative, independent prognostic factor in ESCC and correlates with tumor cell differentiation, vessel permeation, and lymph node metastasis. MMP7, MMP9, and MMP13 may function in early stage ESCC, and their co-expression predicts poor outcome for relatively early stage ESCC patients.

Colorectal Cancer or Colon and Rectal Cancer

Aims: The aim of this study was to compare features of colon and rectal cancers such as prognosis, clinicopathological features and tumor markers, namely carcinoembryonic antigen (CEA), matrix metalloproteinase (MMP)-2 and p27kip1. Methods: Two hundred and thirty patients with stage I–III colon or rectal cancer were retrospectively assessed with the endpoint of recurrence or metastasis after curative operation. CEA, MMP-2 and p27kip1 were studied by immunohistochemistry in cancer tissues of all patients. Results: The disease-free 3-year survival rate after operation of the total 230 patients was 63.0%. The prognosis of colon cancer was significantly better than that of rectal cancer (70.6 vs. 57.0%; p = 0.017), especially for stage III (p = 0.0059). Multivariate analysis also demonstrated that tumor location in the colon or rectum, differentiation, venous invasion and the expression of CEA were independent factors for prognosis. The hazard of recurrence and metastasis in rectal cancer was 1.564 times that in colon cancer. In both groups, there were no statistical differences in age, gender, tumor size, tumor gross type, mucin production, tumor differentiation, venous invasion, MMP-2 and p27kip1. Conclusion: We investigated prognosis, clinicopathological factors, oncogenes and tumor suppressor gene production in colon and rectal cancers. The prognosis of colon cancer is better than that of rectal cancer, especially for stage III. This study shows some differences between colon and rectal cancer.

Resonance Raman and Raman Spectroscopy for Breast Cancer Detection

Raman spectroscopy is a sensitive method to detect early changes of molecular composition and structure that occur in lesions during carcinogenesis. The Raman spectra of normal, benign and cancerous breast tissues were investigated in vitro using a near-infrared (NIR) Raman system of 785 nm excitation and confocal micro resonance Raman system of 532 nm excitation. A total number of 491 Raman spectra were acquired from normal, benign and cancerous breast tissues taken from 15 patients. When the 785 nm excitation was used, the dominant peaks in the spectra were characteristic of the vibrations of proteins and lipids. The differences between the normal and cancerous breast tissues were observed in both the peak positions and the intensity ratios of the characteristic Raman peaks in the spectral region of 700–1800 cm−1. With 532 nm excitation, the resonance Raman (RR) spectra exhibited a robust pattern of peaks within the region of 500–4000 cm−1. The intensities of four distinct peaks at 1156, 1521, 2854 and 3013 cm−1 detected in the spectra collected from normal breast tissue were found to be stronger in comparison with those collected from cancerous breast tissue. The twelve dramatically enhanced characteristic peaks, including the enhanced amide II peak at 1548 cm−1 in the spectra collected from cancerous breast tissue, distinguished the cancerous tissue from the normal tissue. Principal component analysis (PCA) combined with support vector machine (SVM) analysis of the Raman and RR spectral data yielded a high performance in the classification of cancerous and benign lesions from normal breast tissue.

Do young patients with colorectal cancer have a poorer prognosis than old patients

BACKGROUND Colorectal cancer (CRC) is generally a disease of the older population. The prognosis and clinicopathologic features of CRC in the young, compared with those in older patients, continue to be debated. The aim of this study was to compare the survival, clinicopathologic features, and tumor markers of CRC in patients aged 40 y or younger and older patients. METHODS A total of 230 patients with CRC of stage I-III were assessed retrospectively, with an endpoint of recurrence or metastasis after curative operation. The markers CEA, MMP-2, and p27(kip1) were studied by immunohistochemistry in all patients. RESULTS The young group comprised 28 (12.2%) patients aged 40 y or younger with a median age of 36 y. The remaining 202 patients (87.8%) comprised the old group, with a median age of 61 y. There were no statistical differences in gender distribution, tumor sites, tumor size, or gross type between the young and old groups. The young group had a higher incidence of mucinous adenocarcinoma (17.9%) than the old group (6.4%) (P = 0.035). The distribution of stage, differentiation grade, and extent of venous invasion were similar. The median disease-free survival time was 60 mo for the young group and 49 mo for the old. Univariate analysis revealed that this difference was not significant (P = 0.1158). Multivariate Cox regression analysis also demonstrated that the age of the patient was not an independent factor for the prognosis of CRC. There were no statistical differences between the young and old groups in the expression of CEA, MMP-2, or p27(kip1). CONCLUSIONS The results of this study indicated that there was a subtle difference in the incidence of mucinous adenocarcinoma between young and old patients with CRC. However, stage I-III young patients had a similar disease-free survival period as the older patients. Other clinicopathologic characteristics, and tumor markers such as CEA, MMP-2, and p27(kip1), were also similar between young and old CRC patients.

Comparison of carcinoembryonic antigen prognostic value in serum and tumour tissue of patients with colorectal cancer

Objective   Carcinoembryonic antigen (CEA) in the serum and the tumour tissue of colorectal cancer (CRC) patients is the most commonly used tumour marker for the diagnosis and evaluation of prognosis or recurrence after treatment, but the role remains controversial. The objective of this study was to compare the prognostic value of CEA both in serum and tumour tissue in CRC.

Surgical Treatment of Complex Malignant Anterior Mediastinal Tumors Invading the Superior Vena Cava

Determining the appropriate surgery-based treatment for complicated anterior mediastinal malignancies (CAMM), especially those invading the superior vena cava (SVC) and its branches, remains a challenge for general thoracic surgeons. In this report, we summarize our experience and lessons regarding this issue in order to discuss a reasonable strategy for diagnosis and treatment of CAMM. Between January 2001 and April 2003, 15 patients with CAMM invading the SVC and/or its branches with or without invasion of other neighboring organs were surgically treated in our institution by a single surgeon team. We collected clinical data from the medical charts and from surgeons’ specific notes for complicated cases, and performed a comprehensive analysis. There were 9 patients with malignant thymoma. Thymic carcinoma, teratoma, embryonal carcinoma, Hodgkin’s lymphoma, non-Hodgkin’s lymphoma, and mixed teratoma with thymoma were diagnosed in 1 patient each. All procedures were performed via median sternotomy. Some angioplasty techniques were successfully used to resect and reconstruct the SVC. Ten of the 15 patients also underwent pulmonary resection due to involvement of pulmonary parenchyma. Four of the patients underwent perioperative chemotherapy. There were no perioperative deaths. Two patients suffered prolonged ventilation after surgery, and there were no other severe complications related to surgery. One patient died 10 months after surgery. The remaining 14 patients were still living and their progress is still monitored. As of August 2004, the median follow-up duration for all patients was 35 months, and the disease-free survival duration was 10–43 months. CAMM can be safely and completely resected via a median sternotomy, even if it has invaded other mediastinal structures. CAMM should be pathologically identified before initial treatment. A good outcome for patients with CAMM is possible if a suitable strategy combining accurate diagnosis and appropriate treatment, especially surgical resection, is established.

Tissue microarray analysis of multiple gene expression in intestinal metaplasia, dysplasia and carcinoma of the stomach.

Aims : To study multiple gene expression patterns and their roles in the process of gastric carcinogenesis.

Survival Stratification Panel of Colorectal Carcinoma with Combined Expression of Carcinoembryonic Antigen, Matrix Metalloproteinases-2, and p27kip1

PurposeThe prognosis varies greatly in colorectal carcinoma patients, even in the same stage. We examined the association between the expression of matrix metalloproteinases-2, carcinoembryonic antigen, p27kip1, and clinicopathologic features in patients with colorectal carcinoma to identify a possible panel of tumor markers in predicting prognosis of colorectal carcinoma.MethodsThe expressions of three individual markers in 127 colorectal carcinoma cases were analyzed by immunohistochemistry method. Univariate and multivariate analysis were performed to analyze the expression with the disease-free survival time in colorectal carcinoma.ResultsHigh expression of matrix metalloproteinases-2, carcinoembryonic antigen, and low expression of p27kip1 were related to poor prognosis in univariate analysis (P--.0002; P-lt;-.0001; P--.0008). The expression of matrix metalloproteinases-2, carcinoembryonic antigen, p27kip1, and tumor differentiation were independent prognostic factors for disease-free survival by Cox regression analysis. The coexpression panel of matrix metalloproteinases-2, carcinoembryonic antigen, and p27kip had significant prognostic value in all patients (PAB--.0103; PBC--.0068; PCD--.0117). Multivariate analysis with Cox regression reveals that coexpression of matrix metalloproteinases-2, carcinoembryonic antigen, and p27kip1 were independent prognostic factors as tumor differentiation in colorectal carcinoma. In different stages, coexpression tumor markers functioned in Stages II and III but not in the 19 cases of Stage I. The reason might be the number of patients was too small.ConclusionsThe results of this study provided further evidence that the combination of tumor markers of matrix metalloproteinases-2, carcinoembryonic antigen, and p27kip1 was more informative than any single tumor marker alone for the disease-free survival stratification of colorectal carcinoma. Coexpression of matrix metalloproteinases-2, carcinoembryonic antigen, and p27kip1 might be a useful survival stratification panel for clinical management.

Tumor margin detection using optical biopsy techniques

The aim of this study is to use the Resonance Raman (RR) and fluorescence spectroscopic technique for tumor margin detection with high accuracy based on native molecular fingerprints of breast and gastrointestinal (GI) tissues. This tumor margins detection method utilizes advantages of RR spectroscopic technique in situ and in real-time to diagnose tumor changes providing powerful tools for clinical guiding intraoperative margin assessments and postoperative treatments. The tumor margin detection procedures by RR spectroscopy were taken by scanning lesion from center or around tumor region in ex-vivo to find the changes in cancerous tissues with the rim of normal tissues using the native molecular fingerprints. The specimens used to analyze tumor margins include breast and GI carcinoma and normal tissues. The sharp margin of the tumor was found by the changes of RR spectral peaks within 2 mm distance. The result was verified using fluorescence spectra with 300 nm, 320 nm and 340 nm excitation, in a typical specimen of gastric cancerous tissue within a positive margin in comparison with normal gastric tissues. This study demonstrates the potential of RR and fluorescence spectroscopy as new approaches with labeling free to determine the intraoperative margin assessment.

Resonance Raman spectroscopy for human cancer detection of key molecules with clinical diagnosis

Resonance Raman (RR) has the potential to reveal the differences between cancerous and normal breast and brain tissues in vitro. This differences caused by the changes of specific biomolecules in the tissues were displayed in resonance enhanced of vibrational fingerprints. It observed that the changes of reduced collagen contents and the number of methyl may show the sub-methylation of DNA in cancer cells. Statistical theoretical models of Bayesian, principal component analysis (PCA) and support vector machine (SVM) were used for distinguishing cancer from normal based on the RR spectral data of breast and meninges tissues yielding the diagnostic sensitivity of 80% and 90.9%, and specificity of 100% and 100%, respectively. The results demonstrated that the RR spectroscopic technique could be applied as clinical optical pathology tool with a high accuracy and reliability.