Association of ATP7B Mutation Detection Rate with Biochemical Characteristics in Korean Patients with Wilson Disease

Wilson disease (WD) is an autosomal recessive disorder caused by mutations in the ATP7B gene, yet many patients have either one mutation, or no mutation. We investigated whether the mutation detection rate is associated with any biochemical characteristics of WD. In a study of 71 patients, we used PCR-sequencing to screen for ATP7B mutations in 7 exons (exons 8, 10, 11, 14, 15, 16, and 18) covering 95% of known mutations in Korean patients with WD. We also investigated serum concentrations of various biochemical analytes. Data were analyzed by linear association test and one-way ANOVA. Based on the number of detected ATP7B mutations, a significant difference in serum ceruloplasmin concentration was found among the 3 groups (p < 0.001). Serum ceruloplasmin concentration averaged 3.32 +/- 1.74, 10.8 +/- 5.50, and 14.9 +/- 3.88 mg/dl (mean +/- SD) in the 25, 20, and 26 patients with two, one, and no ATP7B mutations, respectively. We observed 82.9% and 16.7% of mutant allele frequency in WD patients with ceruloplasmin concentration < 10 mg/dl and 10-20 mg/dl, respectively (p < 0.001). Thus serum ceruloplasmin concentrations among WD patients differed according to the number of ATP7B mutations detected.Riordan SM, 2001, J HEPATOL, V34, P165Gow PJ, 2000, GUT, V46, P415Brewer GJ, 2009, NETH J MED, V67, P195Korman JD, 2008, HEPATOLOGY, V48, P1167, DOI 10.1002/hep.22446Mak CM, 2008, CLIN CHEM, V54, P1356, DOI 10.1373/clinchem.2008.103432Mak CM, 2008, CRIT REV CL LAB SCI, V45, P263, DOI 10.1080/10408360801991055Park S, 2007, HUM MUTAT, V28, P1108, DOI 10.1002/humu.20574Kroll CA, 2006, MOL GENET METAB, V89, P134, DOI 10.1016/j.ymgme.2006.03.008Durand F, 2001, GUT, V48, P849Yoo HW, 2002, GENET MED, V4, p43S, DOI 10.1097/01.GIM.0000040260.30727.EBSHIM H, 2003, J NUTR, V133, P1527Roberts EA, 2003, HEPATOLOGY, V37, P1475, DOI 10.1053/jhep.2003.50252Ferenci P, 2003, LIVER INT, V23, P139Cullen LM, 2003, CLIN GENET, V64, P429Seo J, 2004, J TURBUL, V5, DOI 10.1088/1468-5248/5/1/015YANG X, 2005, ZHONGHUA NEI KE ZA Z, V44, P13Brewer GJ, 2005, J HEPATOL, V42, pS13, DOI 10.1016/j.jhep.2004.11.013De Bie P, 2005, J HERED, V96, P803, DOI 10.1093/jhered/esi110CHOI JS, 2006, KOREAN J LAB MED, V26, P449Kim JH, 2006, J GASTROEN HEPATOL, V21, P588, DOI 10.1111/j.1440-1746.2005.04127.xEisenbach C, 2007, WORLD J GASTROENTERO, V13, P1711Kenney SM, 2007, HUM MUTAT, V28, P1171, DOI 10.1002/humu.20586Roberts EA, 2008, HEPATOLOGY, V47, P2089, DOI 10.1002/hep.22261Kok KF, 2008, NETH J MED, V66, P348BREWER GJ, 2009, NETH J MED, V67, P196SALLIE R, 1992, HEPATOLOGY, V16, P1206

The invasive lobular carcinoma as a prototype luminal A breast cancer: A retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>Although the invasive lobular carcinoma (ILC) is the second most frequent histologic subtype in Western countries, its incidence is much lower in Asia, and its characteristics are less well known.</p> <p>Methods</p> <p>We assessed the clinical characteristics and outcomes of 83 Korean patients (2.8%) with ILC for comparison with 2,833 (97.2%) with the invasive ductal carcinoma (IDC), including 1,088 (37.3%) with the luminal A subtype (LA-IDC).</p> <p>Results</p> <p>The mean age of all patients was 48.2 years, with no significant differences among the groups. Compared to IDC, ILC showed a larger tumor size (≥T2, 59.8% vs. 38.8%, <it>P </it>= 0.001), a lower histologic grade (HG 1/2, 90.4% vs. 64.4%, <it>P </it>< 0.001), more frequent estrogen receptor positive (90.4% vs. 64.4%, <it>P </it>< 0.001), progesterone receptor positive (71.1% vs. 50.1%, <it>P </it>< 0.001) and HER2 negative (97.5% vs. 74.6%, <it>P </it>< 0.001) status, and lower Ki-67 expression (10.3% ± 10.6% vs. 20.6% ± 19.8%, <it>P </it>< 0.001), as well as being more likely to be of the luminal A subtype (91.4% vs. 51.2%, <it>P </it>< 0.001). Six (7.2%) ILC and 359 (12.7%) IDC patients developed disease recurrence, with a median follow-up of 56.4 (range 4.9-136.6) months. The outcome of ILC was close to LA-IDC (HR 0.77 for recurrence, 95% CI 0.31-1.90, <it>P </it>= 0.57; HR 0.75 for death, 95% CI 0.18-3.09, <it>P </it>= 0.70) and significantly better than for the non-LA-IDC (HR 1.69 for recurrence, 95% CI 1.23-2.33, <it>P </it>= 0.001; HR 1.50 for death, 95% CI 0.97-2.33, <it>P </it>= 0.07).</p> <p>Conclusions</p> <p>ILC, a rare histologic type of breast cancer in Korea, has distinctive clinicopathological characteristics similar to those of LA-IDC.</p