ABSTRACT
BACKGROUND: Bone is the most common site of metastatic breast cancer (MBC). EDTA is often used to decalcify bony tissue samples to ensure the accurate assessment of antigenicity in MBC. It takes ~24 to 48 hours to decalcify small bone tissues such as bone marrow, which is considered unacceptable given the priority that is often placed on the rapid processing of bone marrow trephine cores. Thus, an effective decalcification method that preserves genetic material is needed. AIM: We performed immunohistochemical studies on surface decalcification (SD) in breast tumors and evaluated the effect of SD on receptor status and human epidermal growth factor receptor 2 (HER2). Fluorescence in situ hybridization was performed on a subset of these tumors to establish a protocol for handling bone specimens for MBC. MATERIALS AND METHODS: Forty-four cases of invasive breast tumors were studied. We compared the immunohistochemical expressions of estrogen receptor (ER), progesterone receptor (PR), Ki67, and HER2 between control tissue (nondecalcified) and parallel tissue subjected to SD with hydrochloric acid. We also evaluated the effect of SD on the fluorescence in situ hybridization expression of HER2. RESULTS: Categorical decreases in ER and PR expression were identified in 9/31 (29.0%) cases without SD and 10/26 (38.5%) cases with SD. HER2 expression changed from equivocal to negative in 4/12 (33.4%) cases. Among the HER2-positive cases, all remained positive after SD. The most significant declines in immunoreactivity occurred with Ki67, with an average decrease from 22% to 13%. The average HER2 copy numbers were 5.37 and 4.76 in the control and SD groups, respectively, and the average HER2/CEP17 ratios were 2.35 and 2.08, respectively. CONCLUSIONS: Overall, SD is an alternative decalcification method in bony metastases to assess ER, PR, and HER2 in MBC.
Subject(s)
Breast Neoplasms , Receptors, Estrogen , Humans , Female , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Biomarkers, Tumor/metabolism , Hydrochloric Acid , Ki-67 Antigen/genetics , Immunohistochemistry , In Situ Hybridization, Fluorescence , Receptor, ErbB-2/metabolism , Breast Neoplasms/pathology , EstrogensABSTRACT
Objective:To explore the relationship of CDH17 expression with clinico-pathological features and the correlation be-tween the single nucleotide polymorphisms (SNPs) of CDH17 gene and genetic susceptibility of gastric carcinoma (GC). Methods:A tissue microarray was performed to simulate the dynamic process of invasion and metastasis of GC. Immunohistochemical staining was performed to detect the expression of CDH17 protein, and PCR-based LDR was performed to detect the 2 SNP loci (rs2514813 and rs3214050) genotypes of CDH17 gene. Results: The expression of CDH17 protein in GC was more significantly up-regulated and greatly increased in the intestinal type than in the diffuse type. The expression of CDH17 protein in GC was positively correlated with the histological grading (P0.05). The individuals with the T al-leles had longer survival time than those with the CC genotype (P<0.01). Conclusion:The up-regulation of CDH17 expression is in-volved in the maintenance of histological phenotype and progression of GC. Individuals with T alleles at the CDH17 rs3214050 locus have decreased risk of GC and had better prognosis (OR=0.762, 95%CI:0.619-0.937), thereby suggesting that screening for these alleles would help with the assessment of genetic susceptibility and prognosis of GC in the Fujian population.
ABSTRACT
Objective:To investigate the correlation of Mena protein expression with the invasion and metastasis of Mena SNPs with genetic susceptibility in gastric cancers (GC). Methods:A tissue microarray that simulates the invasion and metastasis process of GC was created, and immunohistochemistry was performed to detect the expression of Mena protein. The Mena gene 5 SNP loci geno-types of 188 healthy people and 389 GC patients were assayed using PCR-based LDR analysis. Results:The expression of Mena pro-tein in GC was significantly upregulated and greatly increased in the intestinal-type and mixed-type GC than that in the diffuse-type and was negatively related to the invasion and metastasis of GC. Patients with Mena overexpression had better prognosis. The frequen-cies of the A and G alleles, as well as the AA, AG, and GG genotypes, at the Mena SNP rs3795443 locus were significantly different be-tween patients with gastric carcinoma and the control groups (OR=2.1489,95%CI 1.4607~3.1613, P<0.01). The frequencies of these five Mena gene SNP loci were not significantly related with the survival of patients with gastric carcinoma. Conclusion:The upregula-tion of Mena expression is involved in maintaining the histological phenotype, invasion, metastasis, and prognosis of gastric adenocarci-noma. Individuals with GG and AG genotypes at the Mena rs3795443 locus have increased risk of gastric carcinoma, which suggests that screening for this genotype would be helpful in assessing the genetic susceptibility of gastric carcinoma.