Comparative study of ROR2 and WNT5a expression in squamous/adenosquamous carcinoma and adenocarcinoma of the gallbladder.

AIM: To investigate the expression and clinical pathological significance of ROR2 and WNT5a in gallbladder squamous/adenosquamous carcinoma (SC/ASC) and adenocarcinoma (AC). METHODS: EnVision immunohistochemistry was used to stain for ROR2 and WNT5a in 46 SC/ASC patients and 80 AC patients. RESULTS: Poorly differentiated AC among AC patients aged > 45 years were significantly more frequent compared with SC/ASC patients, while tumors with a maximal diameter > 3 cm in the SC/ASC group were significantly more frequent compared with the AC group. Positive ROR2 and WNT5a expression was significantly lower in SC/ASC or AC with a maximal mass diameter ≤ 3 cm, a TNM stage of I + II, no lymph node metastasis, no surrounding invasion, and radical resection than in patients with a maximal mass diameter > 3 cm, TNM stage IV, lymph node metastasis, surrounding invasion, and no resection. Positive ROR2 expression in patients with highly differentiated SC/ASC was significantly lower than in patients with poorly differentiated SC/ASC. Positive ROR2 and WNT5a expression levels in highly differentiated AC were significantly lower than in poorly differentiated AC. Kaplan-Meier survival analysis showed that differentiation degree, maximal mass diameter, TNM stage, lymph node metastasis, surrounding invasion, surgical procedure and the ROR2 and WNT5a expression levels were closely related to average survival of SC/ASC or AC. The survival of SC/ASC or AC patients with positive expression of ROR2 and WNT5a was significantly shorter than that of patients with negative expression results. Cox multivariate analysis revealed that poor differentiation, a maximal diameter of the mass ≥ 3 cm, TNM stage III or IV, lymph node metastasis, surrounding invasion, unresected surgery and positive ROR2 or WNT5a expression in the SC/ASC or AC patients were negatively correlated with the postoperative survival rate and positively correlated with mortality, which are risk factors and independent prognostic predictors. CONCLUSION: SC/ASC or AC patients with positive ROR2 or WNT5a expression generally have a poor prognosis.

Jagged1 and DLL4 expressions in benign and malignant pancreatic lesions and their clinicopathological significance.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is characterized by a poor prognosis. Despite intensive research, markers for the early diagnosis, prognosis, and targeting therapy of PDAC are not available. This study aimed to investigate the protein expressions of Jagged1 and DLL4 in PDAC tumor, benign pancreatic and normal pancreatic tissues, and analyze the associations of the two proteins with the clinical and pathological characteristics of PDAC. METHODS: A total of 106 PDAC tumor tissues and 35 peritumoral tissues were collected from January 2000 to December 2011 at our hospitals. Thirteen normal pancreatic tissues and 55 benign pancreatic specimens were collected at the same period. Immunohistochemical staining was used to measure Jagged1 and DLL4 protein expressions in these tissues. RESULTS: The percentage of positive Jagged1 and DLL4 was significantly higher in PDAC than in normal pancreatic tissues, benign pancreatic tissues, and peritumoral tissues (P<0.01). The higher Jagged1 and DLL4 expressions in PDAC were significantly associated with poor differentiation, maximum tumor size >5 cm, invasion, regional lymph node metastasis, and TNM III/IV disease (P<0.05). In PDAC, Jagged1 expression positively correlated with DLL4 expression. Univariate Kaplan-Meier analysis showed that positive Jagged1 and DLL4 expressions were significantly associated with shorter survival in patients with PDAC. Multivariate Cox regression analysis showed that positive Jagged1 and DLL4 expressions were independent prognostic factors for poor prognosis of patients with PDAC. CONCLUSION: Positive Jagged1 and DLL4 expression is closely correlated with severe clinicopathological characteristics and poor prognosis in patients with PDAC.

DNA methylation of hMLH1 correlates with the clinical response to cisplatin after a surgical resection in Non-small cell lung cancer.

Our previous study demonstrated that promoter methylation of human mutL homolog 1 (hMLH1) is involved in determining sensitivity to cisplatin in NSCLC A549/DDP cell line, The present study was designed to determine whether DNA methylation of hMLH1 affects the prognosis of non-small cell lung cancer patients who received cisplatin-based adjuvant chemotherapy. Methylation status of hMLH1 was examined by nested methylation-specific PCR (nested MSP) in 84 archived NSCLC surgically resected tissue specimens from patients receiving cisplatin-based adjuvant chemotherapy. Univariate and multivariate analysis were used to investigate the relationship between hMLH1 methylation status and the clinical prognosis of the patients mentioned above. In the cohort of 84 NSCLC cases, 80 tissue samples were successfully amplified by nested MSP. Among them, 36 samples (45%) were identified to be methylated. Moreover, hMLH1 methylation was not associated with age, gender, smoking status, T stage, histology and differentiation, but correlated with lymphatic metastasis (P=0.021). Multivariate logistic regression analysis showed that hMLH1 methylation may function as a significant independent prognostic factor for tumor recurrence in NSCLC patients treated with adjuvant cisplatin (HR 3.114, 95% CI 1.032-9.399; P=0.044). However, Kaplan-Meier method (P=0.093) and multivariate Cox regression analysis (P=0.598) revealed that hMLH1 methylation was not associated with the survival of these patients. To conclude, the cisplatin-based adjuvant chemotherapy is more beneficial for NSCLC patients without hMLH1 methylation. hMLH1 methylation may have a potential to become a biomarker of individualized therapy for NSCLC patients.

Primary mediastinal large B-cell lymphoma arising from thyroid in a renal recipient with Hashimoto's thyroiditis.

Primary mediastinal large B-cell lymphoma is a subtype of diffuse large B-cell lymphoma, arising in the mediastinum from putative thymic B-cell origin with distinctive clinical and genetic features. Generally, primary mediastinal large B-cell lymphoma is believed as only deriving in the mediastinum. The current study presents a rare case of primary mediastinal large B-cell lymphoma which arising from thyroid in a renal recipient with Hashimoto's thyroiditis. Moreover, we devoted a discussion to the relationship among primary mediastinal large B-cell lymphoma, immunomodulatory therapy and autoimmune diseases. The immunologic derangement induced by long-term immunomodulatory therapy and Hashimoto's thyroiditis may be the possible cause for the ectopic lymphoma.

EphB1 and Ephrin-B, new potential biomarkers for squamous cell/adenosquamous carcinomas and adenocarcinomas of the gallbladder.

Squamous cell/adenosquamous carcinoma (SC/ASC) of the gallbladder are rare tumors and there are few clinical reports in the literature. Herein we report our clinical experience with 46 patients with SC/ASC and 80 with adenocarcinoma (AC). Expression of EphB1 and Ephrin-B in each tumor was determined using immunohistochemical methods for determination of correlations with prognosis. There was no difference in EphB1 and Ephrin-B expression between SC/ASC and AC tumors (P>0.05), but greater expression in those less than 3 cm in diameter, stage I or II (TNM stage), with no lymph node metastases, with no local invasion and treated with radical resection was apparent. Expression of EphB1 (P<0.05) and Ephrin-B (P<0.01) was higher in well differentiated than in poorly differentiated AC tumors. Kaplan-Meier survival analysis indicated that degree of differentiation, tumor diameter, lymph node metastases, local invasion, surgical approach and expression rate of EphB1 and Ephrin-B were closely related to the survival of SC/ASC (P<0.05) and AC patients (P<0.01). Patients with tumors that positive expressed EphB1 and Ephrin-B, whether it is SC/ASC (P SC/ASC =0.000) or AC (P AC =0.000 or P AC =0.002) had longer survival than those negative expression. Cox multivariate analysis indicated a negative correlation between expression of EphB1 or Ephrin-B and overall survival. Hence, EphB1 and Ephrin-B could be regarded as independent good prognostic factorsand important biological markers for SC/ASC and AC of gallbladder.

Pulmonary artery pseudoaneurysm caused by a rare vascular tumor: epithelioid hemangioendothelioma.

We present a case of a 58-year-old female with a rare vascular tumor of intermediate malignancy. The initial manifestation was a pseudoaneurysm caused by the rupture of the right pulmonary artery after tumor invasion. The diagnosis of epithelioid hemangioendothelioma was confirmed by the morphologic and immunocytochemical features after surgery. The patient recovered smoothly and there has been no evidence of local recurrence or metastasis during the 2 years of follow-up.

Gut-lung crosstalk in pulmonary involvement with inflammatory bowel diseases.

Pulmonary abnormalities, dysfunction or hyper-reactivity occurs in association with inflammatory bowel disease (IBD) more frequently than previously recognized. Emerging evidence suggests that subtle inflammation exists in the airways among IBD patients even in the absence of any bronchopulmonary symptoms, and with normal pulmonary functions. The pulmonary impairment is more pronounced in IBD patients with active disease than in those in remission. A growing number of case reports show that the IBD patients develop rapidly progressive respiratory symptoms after colectomy, with failure to isolate bacterial pathogens on repeated sputum culture, and often request oral corticosteroid therapy. All the above evidence indicates that the inflammatory changes in both the intestine and lung during IBD. Clinical or subclinical pulmonary inflammation accompanies the main inflammation of the bowel. Although there are clinical and epidemiological reports of chronic inflammation of the pulmonary and intestinal mucosa in IBD, the detailed mechanisms of pulmonary-intestinal crosstalk remain unknown. The lung has no anatomical connection with the main inflammatory site of the bowel. Why does the inflammatory process shift from the gastrointestinal tract to the airways? The clinical and subclinical pulmonary abnormalities, dysfunction, or hyper-reactivity among IBD patients need further evaluation. Here, we give an overview of the concordance between chronic inflammatory reactions in the airways and the gastrointestinal tract. A better understanding of the possible mechanism of the crosstalk among the distant organs will be beneficial in identifying therapeutic strategies for mucosal inflammatory diseases such as IBD and allergy.

Synchronous occurrence of extramedullary plasmacytoma and squamous cell carcinoma in situ in the larynx: a case report.

Extramedullary plasmacytoma of the larynx is rare, especially when coexisted with squamous cell carcinoma in situ. We report a 56-year-old woman with hoarseness for 6 months and dysphonia for a week. Fiberoptic laryngoscopic examination showed a red, smooth-surface swelling in the submucous region of the left ventricle and ventricular band of the larynx. The patient underwent vertical laryngectomy and modified left neck dissection. Postoperative pathologic examination revealed coexisting plasmacytoma and carcinoma in situ. Bone marrow biopsy and systemic radiogram showed no positive findings. The hepatic and renal functions were normal. Monoclonal immunoglobulin light chain of type kappa was detected in urine. Hence, a laryngeal extramedullary plasmacytoma with carcinoma in situ was diagnosed. No recurrence or progression was observed during a 2-year follow-up. Here, we discussed the risk factors, diagnosis, and therapy for this rare disease.

[Expression and gene mutation of phospho-platelet derived growth factor receptor alpha and C-kit in gastrointestinal and extra-gastrointestinal stromal tumors].

OBJECTIVE: To investigate the expression of phospho-platelet derived growth factor receptor alpha (P-PDGFR-alpha) in gastrointestinal stromal tumors (GIST) and extra-gastrointestinal stromal tumors (EGIST) and its clinical significance. METHODS: Expression of P-PDGFR-alpha in 28 samples of positive CD117 and 13 samples of negative CD117 was detected by Envision immunohistochemical staining. Direct PCR sequencing was used to investigate the mutation status of c-kit gene exons 9, 11, 13, 17 and PDGFR-alpha gene exons 12 and 18. RESULTS: The positive rate of P-PDGFR-alpha expression in GISTs with negative CD117 was 69.2%, which was significantly higher than that in GISTs with positive CD117 (7.1%, P<0.05). The positive rates of P-PDGFR-alpha expression in epithelioid GISTs(27.3%) and mixed GIST(63.3%) were both significantly higher than that in fusiform GISTs (9%, P<0.05). The positive rate of CD117 expression in fusiform GISTs (53.6%)was significantly higher than that in epithelioid GISTs (7.1%) and mixed GISTs(39.3%, P<0.05). C-kit gene mutation was found in 19 GIST cases with positive CD117. C-kit gene mutation was found in 19 of 28 GIST patients with positive CD117, among them, mutation of exon 11 occurred in 15 cases and exon 13 in 4 cases. No C-kit gene mutation was seen in 13 GIST patients with negative CD117. PDGFR-alpha gene mutation was found in 4 of 11 GIST cases with positive P-PDGFR-alpha and all occurred in exon 18. CONCLUSIONS: Examination of P-PDGFR-alpha expression may provide reliable evidence for the further improvement of pathological diagnosis,pathological typing and treatment for GISTs with negative CD117. Phosphorylated protein induced by PDGFR-alpha mutation may be associated with the important alternative molecular mechanism and the biological behavior of GIST development.