Heterogeneity in global gene expression profiles between biopsy specimens taken peri-surgically from primary ER-positive breast carcinomas
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE73237 | GEO | 2016/03/29
SECONDARY ACCESSION(S): PRJNA296671
REPOSITORIES: GEO
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Project description:BackgroundGene expression is widely used for the characterisation of breast cancers. Variability due to tissue heterogeneity or measurement error or systematic change due to peri-surgical procedures can affect measurements but is poorly documented. We studied the variability of global gene expression between core-cuts of primary ER+ breast cancers and the impact of delays to tissue stabilisation due to sample X-ray and of diagnostic core cutting.MethodsTwenty-six paired core-cuts were taken immediately after tumour excision and up to 90 minutes delay due to sample X-ray; 57 paired core-cuts were taken at diagnosis and 2 weeks later at surgical excision. Whole genome expression analysis was conducted on extracted RNA. Correlations and differences were assessed between the expression of individual genes, gene sets/signatures and intrinsic subtypes.ResultsTwenty-three and 56 sample pairs, respectively, were suitable for analysis. The range of correlations for both sample sets were similar with the majority being >0.97 in both. Correlations between pairs for 18 commonly studied genes were also similar between the studies and mainly with Pearson correlation coefficients >0.6 except for a small number of genes, which had a narrow-dynamic range (e.g. MKI67, SNAI2). There was no systematic difference in intrinsic subtyping between the first and second sample of either set but there was c.15 % discordance between the subtype assignments between the pairs, mainly where the subtyping of individual samples was less certain. Increases in the expression of several stress/early-response genes (e.g. FOS, FOSB, JUN) were found in both studies and confirmed findings in earlier smaller studies. Increased expression of IL6, IGFBP2 and MYC (by 17 %, 14 % and 44 %, respectively) occurred between the samples taken 2 weeks apart and again confirmed findings from an earlier study.ConclusionsThere is generally good correlation in gene expression between pairs of core-cuts except where genes have a narrow dynamic range. Similar correlation coefficients to the average gene expression profiles of intrinsic subtype, particularly LumA and LumB, can lead to discordances between assigned subtypes. Substantial changes in expression of early-response genes occur within an hour after surgery and in IL6, IGFB2 and MYC as a result of diagnostic core-cut biopsy.Trial registrationTrial number CRUK/07/015 . Study start date September 2008.
| S-EPMC4818440 | biostudies-literature
Project description:Gene expression is widely used for the characterization of breast cancers. Variability due to tissue heterogeneity or measurement error or systematic change due to peri-surgical procedures can affect measurements but is poorly documented. We studied the variability of global gene expression between core-cuts of primary ER+ breast cancers and the impact of delays to tissue stabilization due to sample x-ray and of diagnostic core-cutting. Twenty-three and 56 sample pairs, respectively, were suitable for analysis. In general, there is a good correlation in gene expression between pairs of core-cuts except where genes have a narrow dynamic range. Increases in the expression of several stress/early-response genes (e.g., FOS, FOSB, JUN) were found in both studies. Substantial changes in expression of early response genes occur within an hour after surgery and in IL6, IGFB2 and MYC as a result of diagnostic core-cut biopsy. Similar correlation coefficients to the average gene expression profiles of intrinsic subtype, particularly LumA and LumB, can lead to discordances between assigned subtypes.
2016-03-29 | GSE73235 | GEO
Project description:Gene expression is widely used for the characterization of breast cancers. Variability due to tissue heterogeneity or measurement error or systematic change due to peri-surgical procedures can affect measurements but is poorly documented. We studied the variability of global gene expression between core-cuts of primary ER+ breast cancers and the impact of delays to tissue stabilization due to sample x-ray and of diagnostic core-cutting. Twenty-three and 56 sample pairs, respectively, were suitable for analysis. In general, there is a good correlation in gene expression between pairs of core-cuts except where genes have a narrow dynamic range. Increases in the expression of several stress/early-response genes (e.g., FOS, FOSB, JUN) were found in both studies. Substantial changes in expression of early response genes occur within an hour after surgery and in IL6, IGFB2 and MYC as a result of diagnostic core-cut biopsy. Similar correlation coefficients to the average gene expression profiles of intrinsic subtype, particularly LumA and LumB, can lead to discordances between assigned subtypes.
2016-03-29 | GSE73236 | GEO
Project description:Heterogeneity in global gene expression profiles between biopsy specimens taken peri-surgically from primary ER-positive breast carcinomas
| PRJNA296671 | ENA
Project description:PIK3CA mutations are expected to be potential therapeutic targets for esophageal squamous cell carcinoma (ESCC). We aimed to clarify the concordance between PIK3CA mutations detected in endoscopic biopsy specimens and corresponding surgically resected specimens.We examined five hotspot mutations in the PIK3CA gene (E542K, E545K, E546K, H1047R, and H1047L) in formalin-fixed and paraffin-embedded tissue sections of paired endoscopic biopsy and surgically resected specimens from 181 patients undergoing curative resection for ESCC between 2000 and 2011 using a Luminex technology-based multiplex gene mutation detection kit.Mutation analyses were successfully performed for both endoscopic biopsy and surgically resected specimens in all the cases. A PIK3CA mutation was detected in either type of specimen in 13 cases (7.2%, 95% confidence interval: 3.9-12.0). The overall concordance rate, positive predictive value, and negative predictive value were 98.3% (178/181), 90.9% (10/11), and 98.8% (168/170), respectively. Among patients with a PIK3CA mutation detected in both types of specimens, the concordance between PIK3CA mutation genotypes was 100%. There were three cases with a discordant mutation status between the types of specimens (PIK3CA mutation in surgically resected specimen and wild-type in biopsy specimen in two cases, and the opposite pattern in one case), suggesting possible intratumoral heterogeneity in the PIK3CA mutation status.The PIK3CA mutation status was highly concordant between endoscopic biopsy and surgically resected specimens from the same patient, suggesting that endoscopic biopsy specimens can be clinically used to detect PIK3CA mutations in patients with ESCC.
| S-EPMC5220610 | biostudies-literature
Project description:BackgroundWe recently reported the clinical significance of intratumoral HER2 heterogeneity on trastuzumab efficacy using surgical specimens; patients with homogeneously HER2 positive gastric cancer benefitted more from trastuzumab. However, the majority of patients are diagnosed by endoscopic biopsy, and surgical specimens are not available in these patients. The aim of this study is to verify clinical significance of HER2 heterogeneity on trastuzumab efficacy using biopsy specimens.MethodsEighty-seven patients, who received trastuzumab-based chemotherapy and whose endoscopic biopsy specimens were available for HER2 assessment, were consecutively enrolled. When all tumor cells in all biopsy specimens overexpressed HER2 protein, it was defined as homogeneously HER2 (homo-HER2) positive group, and the others were defined as heterogeneously HER2 (hetero-HER2) positive group. Progression-free survival (PFS), overall survival (OS) and objective response rate (ORR) were evaluated.ResultsThirty-four patients (39%) were diagnosed as the homo-HER2 group and 53 patients (61%) were the hetero-HER2 group. After the median follow-up period of 17.8 months, the median PFS and OS were 7.6 and 17.8 months, respectively. Significant survival differences were shown between the two groups; the homo-HER2 group showed significantly longer PFS (10.8 vs. 6.1 months, HR 0.469 95% CI 0.29-0.77, p = 0.003) and OS (29.3 vs. 14.4 months, HR 0.352 95% CI 0.20-0.61, p < 0.001). ORR was 68.6% in this cohort. Higher response rate (85.2% vs 58.1%, p = 0.020) and deeper response (- 49.0% vs - 40.0%, p = 0.018) were also found in the homo-HER2 group.ConclusionsSimilar to surgical specimens, we verified clinical significance of HER2 heterogeneity on trastuzumab efficacy using endoscopic biopsy specimens.
| S-EPMC6476840 | biostudies-literature
Project description:Ongoing immunomodulatory strategies in tumors characterized by an overall hot immune phenotype may improve prognosis of head and neck squamous cell carcinomas (HNSCC). Our objective was to develop a reliable and stable scoring system for the identification of immunologically hot HNSCC and to evaluate its association with response to immunotherapies. A Hot Oral Tumor (HOT) score was developed using data from The Cancer Genome Atlas. HOT score was then computed in 27 patients with HNSCC in paired perendoscopic tumor biopsy (initial diagnostic assessment) and subsequent surgically resected specimen. None of the patients was treated with neoadjuvant therapy. Concordance and correlation of the HOT score was high in paired samples.
2022-07-07 | GSE159141 | GEO
Project description:BackgroundER+HER2+ breast cancer requires most types of systemic therapies perioperatively. However, treatment resistance is often experienced. The current study investigated the predictive and prognostic value of intratumoral heterogeneity and conventional clinicopathological factors in patients with ER+HER2+ breast cancer.MethodsThis research included two patient cohorts with ER+HER2+ breast cancer. Cohort A included patients who underwent surgery without neoadjuvant chemotherapy (NAC). Cohort B comprised patients who received NAC followed by surgery. Intratumoral heterogeneity was assessed via ER and HER2 double staining, and the number of cells stained with different patterns of ER and HER2 was counted.ResultsIn total, 11 of 92 tumors in cohort A and four of 45 tumors in cohort B consisted exclusively of double-positive (ER+ and HER2+) cells (homogeneous). The rest had different combinations of cells (heterogeneous). The pathological complete response (pCR) rates differed based on tumoral cell components but not intratumoral heterogeneity. The pCR rate of tumors with ER-HER2+ cells but without HER2- cells was higher than that of others (45.5% vs 4.3%; p = 0.0013). Low ER and PgR Allred scores indicated better pCR rates than high scores (p = 0.0005 and 0.024, respectively). Multivariate analysis showed that the ER Allred score and cell component of ER-HER2+ cells without HER2- cells were independent predictors of pCR (p = 0.0055 and 0.0081, respectively). In cohort B, posttreatment Ki67, but not pCR, was a prognostic factor of DFS and OS (p = 0.028 and 0.017, respectively). The prognostic value of combined posttreatment Ki67 and pCR was superior to that of either alone. Combined pCR and posttreatment Ki67 had an independent prognostic value for DFS and OS (p = 0.0068 and 0.0101, respectively).ConclusionsIn ER+HER2+ breast cancer, the presence of ER-HER2+ cells without HER2- cells was independently associated with pCR. Combined posttreatment Ki67 and pCR can be more precise in predicting prognosis than pCR alone.
| S-EPMC10225233 | biostudies-literature
Project description:Maspin, a member of the serpin family, has a role in cell migration, angiogenesis and apoptosis. Little is known of the clinical significance of maspin gene expression in human cancers. We developed a real-time quantitative RT-PCR assay to quantify the full range of maspin mRNA copy numbers in a series of 10 ER alpha-positive and 10 ER alpha-negative breast tumours. We observed a statistical link between low maspin mRNA levels and positive oestrogen status (P=0.0012). In consequence, to better assess the prognostic value of maspin gene expression in breast cancer, we then quantified maspin mRNA content in an additional independent well-defined cohort of 105 ER alpha-positive postmenopausal breast cancer patients treated with primary surgery followed by adjuvant tamoxifen alone. Maspin expression varied widely in tumour tissues (by nearly four orders of magnitude), being underexpressed in 33 out of 105 tumours (31.4%) and overexpressed in 24 out of 105 tumours (22.9%) relative to normal breast tissues. Immunohistochemical studies demonstrated that maspin protein was strictly expressed in myoepithelial cells of normal breast tissue and in tumour epithelial cells, exclusively in maspin-overexpressing tumours. Patients with tumours overexpressing the maspin gene had significantly shorter relapse-free survival after surgery than patients whose tumours normally expressed or underexpressed maspin (P=0.0011). The prognostic significance of maspin overexpression persisted in Cox multivariate regression analysis (P=0.0024). These findings show that the maspin mRNA level can have important prognostic significance in human breast cancer, and point to the maspin gene as a putative molecular predictor of hormone responsiveness in breast cancer.
| S-EPMC2377080 | biostudies-other
Project description:ObjectivePhotoacoustic (PA) imaging is a novel noninvasive technique that offers high-contrast tomographic imaging with ultrasound-like resolution at depths of centimeters, enabling visualization of deep small vessels. The aim of this pilot study was to survey the characteristics of deep vessel networks in the mucosa of neoplastic gastrointestinal (GI) lesions using PA imaging.MethodsSpecimens of patients who had undergone surgical and endoscopic resection for GI lesions were included in this study. The PA/ultrasound imaging system for clinical research is characterized by a technology that can superimpose a PA image over an ultrasound image. Three-dimensional PA images were acquired for the resected specimen before fixation. The stomach and colon of live pigs were incised, and the walls were scanned from the mucosa.ResultsA total of 32 specimens (nine esophageal, 12 gastric, 11 colorectal) were scanned. The pathological diagnoses were adenomas (n = 2), intramucosal cancers (n = 14), and invasive cancers (n = 16). The deep vessel networks of all lesions could be visualized. In the intramucosal lesions, the deep vessel network was similar to that of a normal tissue. In invasive cancers, the thick and prominent vessel network was visible in the surface layer of esophageal cancers, infiltrated area of gastric cancers, and surface layer and infiltrated area of colorectal cancers. In the images of living pigs, visualizing the vascular network deeper than the submucosa in both the stomach and large intestine was possible.ConclusionOur study confirmed that the deep vessel networks of neoplastic GI lesions were visible by PA imaging.
| S-EPMC8828192 | biostudies-literature