High nevus counts confer a favorable prognosis in melanoma patients

A high number of nevi is the most significant phenotypic risk factor for melanoma and is in part genetically determined. The number of nevi decreases from middle age onward but this senescence can be delayed in patients with melanoma. We investigated the effects of nevus number count on sentinel node status and melanoma survival in a large cohort of melanoma cases. Out of 2,184 melanoma cases, 684 (31.3%) had a high nevus count (>50). High nevus counts were associated with favorable prognostic factors such as lower Breslow thickness, less ulceration and lower mitotic rate, despite adjustment for age. Nevus count was not predictive of sentinel node status. The crude 5‐ and 10‐year melanoma‐specific survival rate was higher in melanomas cases with a high nevus count compared to those with a low nevus count (91.2 vs. 86.4% and 87.2 vs. 79%, respectively). The difference in survival remained significant after adjusting for all known melanoma prognostic factors (hazard ratio [HR] = 0.43, confidence interval [CI] = 0.21–0.89). The favorable prognostic value of a high nevus count was also seen within the positive sentinel node subgroup of patients (HR = 0.22, CI = 0.08–0.60). High nevus count is associated with a better melanoma survival, even in the subgroup of patients with positive sentinel lymph node. This suggests a different biological behavior of melanoma tumors in patients with an excess of nevi.     

Risk factors for thyroid cancer: an epidemiological review focused on nutritional factors

Objectives  The present review summarizes epidemiological evidence on risk factors for thyroid cancer (TC), in particular, nutritional factors. Methods  Searches of articles on the issue were conducted using MEDLINE. Results  Exposure to ionizing radiation, particularly during childhood, is the best-established risk factor for TC. There is also a strong association with history of benign nodules/adenoma or goiter. Iodine deficiency may induce an increasing incidence of benign thyroid conditions, but very high iodine intake also affects thyroid function and, possibly, TC risk. Among dietary factors, fish—the major natural source of iodine in human diet—is not consistently related to TC risk. High intake of cruciferous vegetables shows a weak inverse association with TC. Among other food groups, vegetables other than cruciferous are the only food group showing a favorable effect on TC, with an approximate 20% reduction in risk for subjects with the highest consumption. No effect on TC risk of alcohol, coffee, or other food-groups/nutrients emerged. Height and weight at diagnosis show a moderate positive association with TC risk. Conclusion  At present, the only recognized measures for reducing TC risk is to avoid ionizing radiation and iodine deficiency, particularly in childhood and young women, and to increase vegetable consumption.     

The role of 18F-FDG-PET in the local/regional evaluation of women with breast cancer

Purpose. In women with breast cancer, knowledge of the local/regional extent of the tumor is essential for staging, treatment planning, monitoring response to therapy, and follow-up. Positron emission tomography (PET) is an important imaging test which can detect tumor at multiple sites in women with breast cancer. We compared the ability of PET to provide a comprehensive view of the local/regional extent of tumor in women with stage I, II and stage III, IV breast cancer. Materials and methods. Forty-six women with breast cancer underwent PET using ¹⁸F-FDG. ¹⁸FDG uptake in the breast primary tumor, associated skin, axillary and internal mammary lymph nodes, and the contralateral breast was determined qualitatively, and correlated with histologic, clinical and radiographic findings. Results. Twenty-four patients were premenopausal and 22 were postmenopausal, with the following distribution according to clinical stage: stage I – 2 patients, stage II – 16, stage III – 16, stage IV – 12 patients. Among stage I, II patients, the sensitivity for detection of the primary tumor was 83.3%, and for detection of axillary lymph node metastases was 42.9%. ¹⁸FDG-PET was negative for the breast skin, contralateral breast, and internal mammary lymph nodes in all stage I, II patients, in agreement with clinical and radiographic findings. Among 28 stage III, IV patients, the sensitivity of ¹⁸FDG-PET for detection of the primary tumor was 90.5%, and for detection of axillary lymph node metastases 83.3%. Fourteen patients had clinically advanced changes in the skin, and the sensitivity of PET for detection of skin changes was 76.9%. ¹⁸FDG-PET was positive in the internal mammary lymph nodes in 25.0%, and negative in the contralateral breast in all patients with stage III, IV breast cancer. ¹⁸FDG-PET was studied in 10 patients following neoadjuvant chemotherapy, and showed a strong correlation with clinical response, and with clinical and pathological findings post-treatment at multiple local/regional sites. Conclusion. ¹⁸FDG-PET can provide a comprehensive image of local/regional tumor in women with breast cancer. ¹⁸FDG-PET may play a greater role in women with stage III, IV breast cancer because of increased sensitivity and the increased involvement of multiple local/regional sites with tumor.     

BRCA1 and BRCA2 mutations among breast cancer patients from the Philippines

Age-adjusted incidence rates of breast cancer vary more than 10-fold worldwide, with the highest rates reported in North America and Europe. The highest breast cancer incidence rates in Southeast Asia have been reported for the Manila Cancer Registry in the Philippines, with an age-standardized rate of 47.7 per 100,000 per year. The possible contribution of hereditary factors to these elevated rates has not been investigated. We conducted a case-control study of 294 unselected incident breast cancer cases and 346 female controls from Manila, Philippines. Cases and controls were selected from women below the age of 65 undergoing evaluation at the PGH in Manila because of a suspicious breast mass. Molecular analysis identified 12 BRCA2 mutations and 3 BRCA1 mutations. We estimate the prevalence of BRCA mutations among unselected breast cancer cases in the Philippines to be 5.1% (95% CI: 2.6-7.6%), with a prevalence of 4.1% (95% CI: 1.8-6.4%) for BRCA2 mutations alone. The BRCA2 4265delCT and 4859delA mutations were found in 2 and 4 unrelated cases, respectively; haplotype analysis confirmed that these, and the BRCA1 5454delC mutation, are founder mutations. BRCA2 mutations were also found in 2 of 346 controls (0.6%; 95% CI: 0.2-1.4%). Compared with non-carrier cases, the cumulative risk of breast cancer for first-degree relatives of mutation carriers was 24.3% to age 50, compared with <4% for first-degree relatives of non-carrier cases (RR = 6.6; 95% CI: 2.6-17.2; p= 7.5 x 10(-6)). Our data suggest that penetrance of BRCA mutations is not reduced in the Philippines. Germline mutations in the BRCA2 gene contribute more than mutations BRCA1 to breast cancer in the Philippines, due in large part to the presence of 2 common founder mutations.     

液滴数字PCR 在乳腺癌精准治疗中的应用

在精准医学大背景下,分子分型指导下的乳腺癌个体化治疗虽已成为常态,但仍需不断寻求更加优质高效的精准治疗方案。液滴数字PCR（droplet digital PCR,ddPCR）在稀有基因突变检测、拷贝数变异检测以及与下一代测序技术相整合等方面,较传统的实时荧光定量PCR表现出明显的优势。本文针对ddPCR平台在不同乳腺癌亚型中的应用,以及对ddPCR技术助力下的乳腺癌的研究进行综述。      

ITV-Based Robust Optimization for VMAT Planning of Stereotactic Body Radiation Therapy of Lung Cancer

Purpose

Using planning target volume (PTV) to account for setup uncertainties in stereotactic body radiation therapy (SBRT) of lung cancer has been questioned because a significant portion of the PTV contains low-density lung tissue. The purpose of this study is to (1) investigate the feasibility of using robust optimization to account for setup uncertainties in volumetric modulated arc therapy plan for lung SBRT and (2) evaluate the potential normal tissue–sparing benefit of a robust optimized plan compared with a conventional PTV-based optimized plan.

沉默 Med19 的表达对结肠癌Caco-2细胞增殖和凋亡的影响

目的：探讨RNA干扰 Med19 的表达对结肠癌Caco-2细胞增殖和凋亡的影响。 方法: 构建靶向 Med19 的干扰质粒pSilencer-Med19-siRNA,转染Caco-2细胞后,RT-PCR检测Caco-2细胞中 Med19 mRNA的表达,Western blotting检测Caco-2细胞中Med19蛋白的表达,MTT检测pSilencer-Med19-siRNA转染后Caco-2细胞的增殖,流式细胞术分析Caco-2细胞的凋亡。 结果: RT-PCR及Western blotting检测结果显示,pSilencer-Med19-siRNA转染后Caco-2细胞中 Med19 mRNA及蛋白表达水平上均显著下降（P<0.01）;MTT及流式细胞术检测结果表明,与pSilencer对照组相比,pSilencer-Med19-siRNA组Caco-2细胞的增殖明显受到抑制\[7 d时：（0.86±0.09）% vs（1.38±1.10）%,P<0.01\],且细胞凋亡比例明显升高\[（22.72±2.85）% vs（7.23±1.29）%,P<0.01\]。 结论: RNA干扰沉默 Med19 的表达可抑制结肠癌Caco-2细胞的增殖,促进其凋亡,提示 Med19 可作为结肠癌治疗的潜在靶点。