Determination of Tumor Heterogeneity in Colorectal Cancers Using Heterogeneity Tissue Microarrays
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Determination of Tumor Heterogeneity in Colorectal Cancers Using Heterogeneity Tissue Microarrays. / Stahl, Phillip R; Schnellert, J; Koop, Christina; Simon, Ronald; Marx, Andreas; Izbicki, Jakob R; Sauter, Guido; Quaas, Alexander.
in: PATHOL ONCOL RES, Jahrgang 21, Nr. 4, 09.2015, S. 1183-9.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Determination of Tumor Heterogeneity in Colorectal Cancers Using Heterogeneity Tissue Microarrays
AU - Stahl, Phillip R
AU - Schnellert, J
AU - Koop, Christina
AU - Simon, Ronald
AU - Marx, Andreas
AU - Izbicki, Jakob R
AU - Sauter, Guido
AU - Quaas, Alexander
PY - 2015/9
Y1 - 2015/9
N2 - Cancer is often heterogeneous both on a morphological and on a genetic level. Though resected tumors are often large, molecular tumor analysis is usually restricted to one tissue block. In this project we introduce a new tool for a high-throughput heterogeneity analysis of colorectal cancer. A heterogeneity tissue microarray (TMA) was manufactured from tissues of 340 patients with colorectal cancer. For this purpose 8 different tissue spots were taken from as many different cancer blocks per patient as possible (at least 4 different blocks). Additional tissue samples from 1 to 4 corresponding lymph node metastases were added from 134 patients. The system was then validated by analysing one parameter each known for minimal (p53) or substantial (HER2) heterogeneity in colorectal cancer. P53 alterations as detected by immunohistochemistry were seen in 174 (51.3 %) of 339 analyzable primary tumors of which 23 (13.2 % of positive cases) showed a heterogeneous distribution pattern. HER2 overexpression was seen in 18 (5.4 %) of 336 evaluable tumors. HER2 amplification occurred in 6 (33.3 %) of the 18 cases with HER2 overexpression. Genomic heterogeneity was more prevalent for HER2 alterations than for p53 alterations. For immunohistochemical expression analysis, 16 of 18 positive cases were heterogeneous (88.9 %) and for amplification 3 of 6 cases (50 %) were heterogeneous. Large section validation revealed, however a considerable fraction of heterogeneous cases were due to technical artifacts. In summary, our data suggest, that heterogeneity TMAs are a powerful tool to rapidly screen for molecular heterogeneity in colorectal cancer.
AB - Cancer is often heterogeneous both on a morphological and on a genetic level. Though resected tumors are often large, molecular tumor analysis is usually restricted to one tissue block. In this project we introduce a new tool for a high-throughput heterogeneity analysis of colorectal cancer. A heterogeneity tissue microarray (TMA) was manufactured from tissues of 340 patients with colorectal cancer. For this purpose 8 different tissue spots were taken from as many different cancer blocks per patient as possible (at least 4 different blocks). Additional tissue samples from 1 to 4 corresponding lymph node metastases were added from 134 patients. The system was then validated by analysing one parameter each known for minimal (p53) or substantial (HER2) heterogeneity in colorectal cancer. P53 alterations as detected by immunohistochemistry were seen in 174 (51.3 %) of 339 analyzable primary tumors of which 23 (13.2 % of positive cases) showed a heterogeneous distribution pattern. HER2 overexpression was seen in 18 (5.4 %) of 336 evaluable tumors. HER2 amplification occurred in 6 (33.3 %) of the 18 cases with HER2 overexpression. Genomic heterogeneity was more prevalent for HER2 alterations than for p53 alterations. For immunohistochemical expression analysis, 16 of 18 positive cases were heterogeneous (88.9 %) and for amplification 3 of 6 cases (50 %) were heterogeneous. Large section validation revealed, however a considerable fraction of heterogeneous cases were due to technical artifacts. In summary, our data suggest, that heterogeneity TMAs are a powerful tool to rapidly screen for molecular heterogeneity in colorectal cancer.
U2 - 10.1007/s12253-015-9953-4
DO - 10.1007/s12253-015-9953-4
M3 - SCORING: Journal article
C2 - 26026893
VL - 21
SP - 1183
EP - 1189
JO - PATHOL ONCOL RES
JF - PATHOL ONCOL RES
SN - 1219-4956
IS - 4
ER -