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Histological and molecular evaluation of patient-derived colorectal cancer explants.

Uronis JM, Osada T, McCall S, Yang XY, Mantyh C, Morse MA, Lyerly HK, Clary BM, Hsu DS - PLoS ONE (2012)

Bottom Line: However, it remains unclear to what extent explanted colorectal tumor tissues retain inherent pathological features over time.Using this panel, we performed a comparison of histology, gene expression and mutation status between PDCCEs and the original human tissues from which they were derived.Our findings demonstrate that PDCCEs maintain key histological features, basic gene expression patterns and KRAS/BRAF mutation status through multiple passages.

View Article: PubMed Central - PubMed

Affiliation: Institute for Genome Sciences and Policy, Duke University, Durham, North Carolina, United States of America.

ABSTRACT
Mouse models have been developed to investigate colorectal cancer etiology and evaluate new anti-cancer therapies. While genetically engineered and carcinogen-induced mouse models have provided important information with regard to the mechanisms underlying the oncogenic process, tumor xenograft models remain the standard for the evaluation of new chemotherapy and targeted drug treatments for clinical use. However, it remains unclear to what extent explanted colorectal tumor tissues retain inherent pathological features over time. In this study, we have generated a panel of 27 patient-derived colorectal cancer explants (PDCCEs) by direct transplantation of human colorectal cancer tissues into NOD-SCID mice. Using this panel, we performed a comparison of histology, gene expression and mutation status between PDCCEs and the original human tissues from which they were derived. Our findings demonstrate that PDCCEs maintain key histological features, basic gene expression patterns and KRAS/BRAF mutation status through multiple passages. Altogether, these findings suggest that PDCCEs maintain similarity to the patient tumor from which they are derived and may have the potential to serve as a reliable preclinical model that can be incorporated into future strategies to optimize individual therapy for patients with colorectal cancer.

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Related in: MedlinePlus

PDCCE tumor pathology is retained after 11 generations in mice.H&E stained sections of two independent well-differentiated adenocarcinomas (CRC039 and CRC075) show that tumor architecture remains similar after 11 passages in NOD/SCID mice. Images shown are at 20× magnification.
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pone-0038422-g001: PDCCE tumor pathology is retained after 11 generations in mice.H&E stained sections of two independent well-differentiated adenocarcinomas (CRC039 and CRC075) show that tumor architecture remains similar after 11 passages in NOD/SCID mice. Images shown are at 20× magnification.

Mentions: A panel of 27 patient-derived colorectal cancer explants (PDCCEs) by direct transplantation of human colorectal cancer (CRC) tissues into NOD-SCID mice was created in this study. Table 1 shows the origin of the patient tumor and a total of 5 primary PDCCEs and 22 metastatic PDCCEs were generated. To assess the extent to which in vivo models of patient-derived colorectal cancer explants (PDCEEs) accurately recapitulate and can therefore serve as a model of the human condition, we investigated whether PDCCEs retain key biological features inherent to individual human colorectal cancers (CRC) over time. First, to evaluate the extent to which histological parameters are retained after xeno-transplantation, two independent PDCCEs were passaged through >10 generations and evaluated histologically. Both PDCCEs examined exhibited pathological features remarkably consistent with the original patient tumor through 11 generations (Figure 1). Next, a comprehensive histological evaluation performed on a sub-panel of 15 matched PDCCEs and original banked tissues revealed that 15/15 PDCCEs retained pathological features similar to those observed in the matched human tumor and were characterized as histologically identical to their matched original banked sample (Table 2). Even after 11 generations, PDCCEs retained the ability to form glands and contained CDX-2 positive nuclei comparable to the first generation PDCCEs (Figure 2). These data demonstrate that the histological features present in colorectal cancer, including the formation of glands and presence of stromal components are retained even in late passage explants, suggesting that unlike CRC cell line-derived xenografts, the PDCCE model provides us with a research tool that recapitulates the human condition generally not observed in other models.


Histological and molecular evaluation of patient-derived colorectal cancer explants.

Uronis JM, Osada T, McCall S, Yang XY, Mantyh C, Morse MA, Lyerly HK, Clary BM, Hsu DS - PLoS ONE (2012)

PDCCE tumor pathology is retained after 11 generations in mice.H&E stained sections of two independent well-differentiated adenocarcinomas (CRC039 and CRC075) show that tumor architecture remains similar after 11 passages in NOD/SCID mice. Images shown are at 20× magnification.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3366969&req=5

pone-0038422-g001: PDCCE tumor pathology is retained after 11 generations in mice.H&E stained sections of two independent well-differentiated adenocarcinomas (CRC039 and CRC075) show that tumor architecture remains similar after 11 passages in NOD/SCID mice. Images shown are at 20× magnification.
Mentions: A panel of 27 patient-derived colorectal cancer explants (PDCCEs) by direct transplantation of human colorectal cancer (CRC) tissues into NOD-SCID mice was created in this study. Table 1 shows the origin of the patient tumor and a total of 5 primary PDCCEs and 22 metastatic PDCCEs were generated. To assess the extent to which in vivo models of patient-derived colorectal cancer explants (PDCEEs) accurately recapitulate and can therefore serve as a model of the human condition, we investigated whether PDCCEs retain key biological features inherent to individual human colorectal cancers (CRC) over time. First, to evaluate the extent to which histological parameters are retained after xeno-transplantation, two independent PDCCEs were passaged through >10 generations and evaluated histologically. Both PDCCEs examined exhibited pathological features remarkably consistent with the original patient tumor through 11 generations (Figure 1). Next, a comprehensive histological evaluation performed on a sub-panel of 15 matched PDCCEs and original banked tissues revealed that 15/15 PDCCEs retained pathological features similar to those observed in the matched human tumor and were characterized as histologically identical to their matched original banked sample (Table 2). Even after 11 generations, PDCCEs retained the ability to form glands and contained CDX-2 positive nuclei comparable to the first generation PDCCEs (Figure 2). These data demonstrate that the histological features present in colorectal cancer, including the formation of glands and presence of stromal components are retained even in late passage explants, suggesting that unlike CRC cell line-derived xenografts, the PDCCE model provides us with a research tool that recapitulates the human condition generally not observed in other models.

Bottom Line: However, it remains unclear to what extent explanted colorectal tumor tissues retain inherent pathological features over time.Using this panel, we performed a comparison of histology, gene expression and mutation status between PDCCEs and the original human tissues from which they were derived.Our findings demonstrate that PDCCEs maintain key histological features, basic gene expression patterns and KRAS/BRAF mutation status through multiple passages.

View Article: PubMed Central - PubMed

Affiliation: Institute for Genome Sciences and Policy, Duke University, Durham, North Carolina, United States of America.

ABSTRACT
Mouse models have been developed to investigate colorectal cancer etiology and evaluate new anti-cancer therapies. While genetically engineered and carcinogen-induced mouse models have provided important information with regard to the mechanisms underlying the oncogenic process, tumor xenograft models remain the standard for the evaluation of new chemotherapy and targeted drug treatments for clinical use. However, it remains unclear to what extent explanted colorectal tumor tissues retain inherent pathological features over time. In this study, we have generated a panel of 27 patient-derived colorectal cancer explants (PDCCEs) by direct transplantation of human colorectal cancer tissues into NOD-SCID mice. Using this panel, we performed a comparison of histology, gene expression and mutation status between PDCCEs and the original human tissues from which they were derived. Our findings demonstrate that PDCCEs maintain key histological features, basic gene expression patterns and KRAS/BRAF mutation status through multiple passages. Altogether, these findings suggest that PDCCEs maintain similarity to the patient tumor from which they are derived and may have the potential to serve as a reliable preclinical model that can be incorporated into future strategies to optimize individual therapy for patients with colorectal cancer.

Show MeSH
Related in: MedlinePlus