Lower and reduced expression of EphA4 is associated with advanced TNM stage, lymph node metastasis, and poor survival in breast carcinoma.

The expression of EphA4 has been well documented in the development of nerve and in certain types of human cancer. Few studies of EphA4, however, have focused on breast carcinoma. In this study, a set of breast carcinomas was subjected to immunohistochemical staining. In normal luminal cells, EphA4 was weakly detected in 11 (14.3 %), moderately detected in 15 (19.5 %) and highly detected in 51 out of 77 (66.2 %) samples, while in breast carcinoma cells, EphA4 was weakly detected in 42 (54.5 %), moderately detected in 19 (24.7 %) and highly detected in 16 out of 77 (20.8 %) samples (P < 0.001). The expression of EphA4 protein was significantly reduced in 68.8 % of breast carcinoma samples comparing with normal cells. The expression of EphA4 was significantly associated with tumor grade (P = 0.003), TNM stage (P = 0.034), lymph node metastasis (P = 0.034) and Ki-67 (P < 0.001). No significant relationship was found between the expression of EphA4 and age, molecular subtypes, and HER2 status. Survival analysis showed that significant association of low expression of EphA4 in tumor cells with short overall survival (P = 0.048) and disease-free survival (P = 0.051). Our data show that EphA4 was reduced in breast carcinoma, which is associated with high grade, advanced TNM stage, lymph node metastasis, and poor outcome of patients.

Relationship between gastric cancer tau protein expression and paclitaxel sensitivity.

The abnormal expression of Tau protein in breast cancer tissue affects paclitaxel sensitivity. The abnormal expression also exists in gastric carcinoma. Therefore, we speculate that the expression levels of Tau protein is closely related to paclitaxel sensitivity in gastric cancer, thus affecting the efficacy of paclitaxel. In this study, we used immunohistochemical methods to detect Tau protein expression levels in 47 cases of gastric cancer specimens. We also used Western blot to detect the level of Tau protein expression in gastric cancer cell lines and to check the efficacy of paclitaxel in vitro application. Findings indicate that Tau protein expression rate can reach as high as (+ +-+ + +) 63.83 % in gastric cancer. Paclitaxel induces inhibition and apoptosis with low expression of Tau protein in gastric cancer cell lines (P < 0.05). The level of Tau protein expression is significantly correlated with paclitaxel efficacy. If confirmed by further studies, the Tau protein can be another useful marker of gastric cancer, thereby leading to the application of paclitaxel in cancer treatment.

Expression and significance of Six1 and Ezrin in cervical cancer tissue.

This study aimed to investigate the expression of Six1 gene and its downstream target gene Ezrin in cervical cancer, and to correlate their expression to the clinical pathology of cervical cancer. RT-PCR and Western blot were used to detect the expression of Six1 and Ezrin in cervical cancer tissue, cervical intraepithelial neoplasia tissue, and normal cervical tissue. The correlation of Six1 and Ezrin expression with the occurrence, development, and clinical pathology of cervical cancer was then analyzed. The expression of Six1 and Ezrin mRNA and protein in cervical cancer and cervical intraepithelial neoplasia was significantly higher than in normal cervical tissue (p < 0.05). Their expression was also significantly higher in the cancerous tissues of patients with advanced cervical cancer than in those of patients with early-stage cervical cancer (p < 0.05). Moreover, they were expressed at significantly higher levels in lymph node metastasis-positive patients than in lymph node metastasis-negative patients (p < 0.05). Finally, we observed that lesser differentiated tumors had elevated expression of Six1 and Ezrin mRNA and protein (p < 0.05). However, the mRNA and protein expression of Six1 and Ezrin were independent of patient age and tumor size (p > 0.05). Further investigation is warranted to describe the relation of whether Six1 and Ezrin protein contributes to the mechanism of occurrence, development, differentiation, and invasiveness of the tumor. These markers could be used as indicators of prognosis in early-stage cervical cancer as Six1 and Ezrin had a synergistic effect on the incidence of cervical cancer.

[Clinicopathological analysis of 250 patients with early-stage gastric cancer].

OBJECTIVE: To explore the factors associated with early diagnosis of gastric cancer. METHODS: Clinical data were retrospectively analyzed for 250 patients with early-stage gastric cancer (EGC) from 2005 to 2008, during which the concept of intra-epithelial neoplasia (IN) was adopted in our department. RESULTS: On preoperative endoscopic biopsy with pathological exam, there were 15 cases suspicious for cancer, 90 with high-grade IN (HGIN), and 15 gastric cancer. Postoperative pathological exam of the surgical specimen showed infiltrating early-stage cancer in 224 patients, of which 5 (2.2%) were type I (all were Tsm), 190 (84.8%) were type II including Tm in 82 and Tsm in 108 patients, 29 were type III (5 Tm and 24 Tsm). Twenty-six patients had non-infiltrating lesions (Tis). There were 184 (73.6%) well-differentiated tumors, including 26 Tis, 58 Tm, and 100 Tsm. Lymphatic metastasis was identified in 21 patients, of which 2 (2.3%) were Tm (all were poorly-differentiated) and 19 (13.9%) were Tsm. Lymphadenopathy was present in 15 (7.9%) cases in type II, and in 6 (20.7%) in type III. Of the 90 cases with a preoperative diagnosis of HGIN, 24 were found to be Tis, 29 were Tm, and 37 were Tsm on postoperative pathological assessment. CONCLUSIONS: Well-differentiation is the main histological type in EGC. The adoption of the concept of IN is associated with improved detection of EGC, which warrants further investigation.

Improved marking and characterizing of pulmonary nodules on digital radiographs using a computer-aided diagnosis system.

OBJECTIVE: To evaluate and reduce inter-observer variations in the detection and characterization of pulmonary nod-ules on digital radiograph (DR) chest images. METHODS: Two hundreds and thirty-two new posterior-anterior DR chest images were collected from out-patient screening patients. Consensus was reached by two experienced radiologists on the marking, rating, and segmentation of small actionable nodules ranged from 5 to 15 mm in diameter using a computer-aided diagnosis (CAD) system. Both their own nodule findings and the computer's automatic nodule detection results were analyzed to make the consensus. Nodules identified together with corresponding likelihood rating and segmentation results were referred as "Gold Standard". Two un-experienced radiologists were asked to first mark and characterize suspicious nodules independently, then were allowed to consult the computer nodule detection results and change their decisions. RESULTS: Large inter-observer variations in pulmonary nodule identification and characterization on DR chest images were observed between un-experienced radiologists. Un-experienced radiologists could greatly benefit from the CAD system, including substantial decrease of inter-observer variation and improvement of nodule detection rates. Moreover, radiologists with different levels of skillfulness could achieve similar high level performance after using the CAD system. CONCLUSION: The CAD system shows a high potential for providing a valuable assistance to the examination of DR chest images.

Inter-observer variations of digital radiograph pulmonary nodule marking by using computer toolkit.

OBJECTIVE: To assess inter-observer variations of pulmonary nodule marking in routine clinical chest digital radiograph (DR) softcopy reading by using a lung nodule computer toolkit. METHODS: A total of 601 chest posterior-anterior DR images were randomly selected from routine outpatient screening in Peking Union Medical College Hospital. Two chest radiologists with experience more than ten years were first asked to read the images and mark all suspicious nodules independently by using computer toolkit IQQA-Chest, and to indicate the likelihood for each nodule detected. They were also asked to draw the boundary of the identified nodule manually on an enlarged region of interest, which was instantly analyzed by IQQA-Chest. Two sets of diagnostic reports, including the marked nodules, likelihood, manually drawn boundaries, quantitative measurements, and radiologists' names, were automatically generated and stored by the computer system. One week later, the two radiologists read the same images together by using the same computer toolkit without referring to their previous reading results. Marking procedure was the same except that consensus was reached for each suspicious region. Statistical analysis tools provided in the IQQA-Chest were used to compare all the three sets of reading results. RESULTS: In the independent readings, Reader 1 detected 409 nodules with a mean diameter of 12.4 mm in 241 patients, and Reader 2 detected 401 nodules with a mean diameter of 12.6 mm in 253 patients. In the consensus reading, a total of 352 nodules with a mean diameter of 12.4 mm were detected in 220 patients. Totally, 42.3% of Reader 1's and 45.1% of Reader 2's marks were confirmed by the consensus reading. About 40% of each reader's marks agreed with the other. There were only 130 (14.4%) out of the total 904 unique nodules were confirmed by both readers and the consensus reading. Moreover, 5.6% (51/904) of the marked regions were rated identical likelihood in all three readings. Statistical analysis showed significant differences between Readers 1 and 2, and between consensus and Reader 2 in determining the likelihood of the marks (P < 0.01), but not between consensus and Reader 1. No significant difference in terms of size was observed in nodule segmentation between either two of the three readings. CONCLUSION: Large variations in nodule marking and nodule-likelihood determination but not in nodule size were observed between experts as well as between single-person reading and consensus reading.