Maopeng Yang

The First Case of Omental Metastasis from Primary Choroidal Melanoma

Choroidal melanoma is the most common intraocular malignancy and can be fatal in half of the patients because of metastatic disease. Metastasis of choroidal melanoma to the omentum is extremely rare and, to our knowledge, no such case has ever been described in the literature. Here we present a 41-year-old Chinese man with an omental metastasis, 5 years after he was diagnosed with a spindle-cell-type malignant melanoma of the choroid and had his left eye enucleated. The patient demonstrated some uncommon symptoms, but the diagnosis was confirmed histopathologically. The cells were positive for S-100, HMB-45 and Melan-A proteins. He underwent a complete tumor resection and concomitantly received chemotherapy, biological treatment and traditional Chinese medicine. At 2-year follow-up, this patient continues to do well.

Beclin 1 and LC3 as predictive biomarkers for metastatic colorectal carcinoma

Autophagy is a highly conserved self-destructive process that disassembles dysfunctional or unnecessary cellular components. It plays an important role in cancer metastasis, which is of particular interest considering metastatic disease is the major cause of colorectal carcinoma (CRC) related mortality. Here, we investigated the immunohistochemical expression of autophagy-related protein Beclin 1 and Microtubule-associated protein 1A/1B-light chain 3 (LC3) within surgical CRC specimens, first in a training cohort (205 patients), then in an inner validation cohort (160 patients) and an independent cohort (161 patients). The expressions of Beclin 1 and LC3 were lower in metastatic CRC compared with non-metastatic CRC. Furthermore, we developed an autophagy-based classifier for metastatic prediction. This classifier, including Beclin 1, LC3 and carcinoembryonic antigen (CEA) level, resulted in 82.9% sensitivity and 89.8% specificity for metastatic detection in the training cohort. In the independent cohort, it achieved 77.9% sensitivity and 90.3% specificity in predicting the metastasis of CRC. These results suggested that low expression of Beclin 1 and LC3 contributed to a more aggressive cancer cell phenotype, and our autophagy-based classifier was a reliable tool for metastatic prediction in CRC.

Efficacy of epidermal growth factor receptor inhibitors in combination with chemotherapy in advanced non-small cell lung cancer: A meta-analysis of randomized controlled trials

The role of a combination of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and chemotherapy for non-small-cell lung cancer (NSCLC) has not been well established. To clarify this problem, we performed a meta-analysis with 15 studies identified from PubMed, EMBASE and the Cochrane Library. We found that the combined regimen had a significant benefit on progression-free survival (PFS) (hazard ratio (HR) = 0.80; 95% CI = 0.71–0.90; P < 0.001) and the objective response rate (ORR) (RR = 1.35; 95% CI = 1.14–1.59; P < 0.001). However, the combined regimen had no significant impact on overall survival (OS) (HR = 0.96; 95% CI = 0.90–1.03; P = 0.25). Subgroup analysis showed significantly higher OS advantages in EGFR mutation positive patients (P = 0.01), never smokers (P = 0.01), Asian patients (P = 0.02), patients receiving second-line treatment (P < 0.001), and those receiving a sequential combination of EGFR-TKIs and chemotherapy (P = 0.005). The combination regimen showed a higher incidence of grade 3–4 toxicities (leucopenia, neutropenia, febrile neutropenia, anemia, rash, fatigue and diarrhea). In summary, the combination of EGFR-TKIs plus chemotherapy in advanced NSCLC achieved a significantly longer PFS and a higher ORR but not longer OS. Well-designed prospective studies are needed to confirm these findings.

Risk factors of recurrence in small-sized, node negative breast cancer in young women: a retrospective study in Chinese population

We aimed to investigate risk factors of local and distant recurrence in small-sized, node negative breast cancer in women <35 years in a Chinese cohort. Between January 1994 and January 2007, 107 patients with pathologically confirmed small-sized (⩽1 cm), node negative breast cancer who did not receive neoadjuvant or adjuvant chemotherapy were included. The 5-year recurrence-free survival (RFS) was estimated according to different prognostic variables. With a median time of 60 months (range, 8–60 months) follow-up, local and distant recurrence were observed in 25 cases (23.4%). By univariate analysis, HER-2 positivity, triple negative (TN), and high Ki-67 index (⩾14%) were risk factors of a lower RFS (hazard ratio (HR) 6.680, 95% confidence interval (CI) 2.350–18.985, P<0.0001 for HER-2 positive; HR 4.769, 95%CI 1.559–14.591, P=0.006 for TN; HR 6.030, 95%CI 2.659–13.674, P<0.0001 for high Ki-67 index). Patients with grade 3 tumors had a lower RFS (HR 2.922, 95%CI 1.096–7.791, P=0.032) compared with those with grade 1 or grade 2 tumors. By multivariate analysis, HER-2 positivity (HR 10.204, 95%CI 3.391–30.704, P<0.0001), TN (HR 10.521, 95% CI 3.152–35.113, P<0.0001) and high Ki-67 index (HR 10.820, 95%CI 4.338–27.002, P<0.0001) remained risk factors of RFS. In this cohort, HER-2 positivity, triple negative and high Ki-67 index were independent risk factors of RFS in young patients with T1a,bN0 breast cancer. Subsequent pregnancy did not affect RFS.

Methylation of DACT2 contributes to the progression of breast cancer through activating WNT signaling pathway

The activation of the Wnt/β-catenin signaling pathway has been demonstrated to play important roles in breast carcinogenesis and to be associated with a poorer prognosis in breast cancer patients. However, genetic mutation is not the major reason for Wnt/β-catenin activation in breast cancer. Dishevelled-associated antagonist of β-catenin homolog 2 (DACT2) is a negative regulator of β-catenin and acts as a tumor suppressor in numerous cancer types; however, the expression change and potential role of DACT2 in breast cancer is unknown. The present study detected the expression and function of DACT2 in breast cancer progression. It was identified that the expression of DACT2 significantly decreased in breast cancer tissues compared with paired adjacent normal breast tissues. Additional investigation demonstrated that the hypermethylation of DACT2 gene promoter contributes to the loss of the gene in breast cancer. It was also demonstrated that DACT2 is a tumor suppressor in breast cancer and inhibits the proliferation and invasion of breast cancer cells by repressing the expression of β-catenin target genes associated with tumor growth and metastasis. The present study indicates that the loss of DACT2 may contribute to breast cancer progression and provides a promising therapeutic target for the treatment of breast cancer.