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Human thyroid tumours, the puzzling lessons from E7 and RET/PTC3 transgenic mice.

Jin L, Burniat A, Dumont JE, Miot F, Corvilain B, Franc B - Br. J. Cancer (2008)

Bottom Line: There is an 'oncogene dependent' cellular signature, maintained at all studied ages in the E7 model, less in the RET/PTC3 model.The Tg-E7 model was less heterogeneous, with a dominant goitrous pattern.The solid tumour already described in the RET/PTC3 models associated with cribriform patterns, suggested 'PTC spindle cell changes' as in humans PTC rather than the equivalent of the solid human PTC.

View Article: PubMed Central - PubMed

Affiliation: Institut de Recherche Interdisciplinaire (IRIBHM), Faculté de Médecine, Université Libre de Bruxelles (ULB), Campus Erasme, Route de Lennik 808, B 1070 Bruxelles, Belgique. lingjin@ulb.ac.be

ABSTRACT
Human rearranged RET/PTC3 (papillary thyroid carcinoma) proto-oncogene and high-risk human papillomavirus (HPV) type 16 E7 oncogene induces in the mouse a neoplastic transformation of thyroid follicular cells. We present a detailed immuno-histological study (170 mouse thyroids: RET/PTC3, E7, wild type, 2- to 10-month-old) with cell cycle proliferation and signalling pathway indicators. The characteristics of both models are different. There is an 'oncogene dependent' cellular signature, maintained at all studied ages in the E7 model, less in the RET/PTC3 model. During tumour development a large heterogeneity occurred in the Tg-RET/PTC3 model within a same tumour or within a same thyroid lobe. The Tg-E7 model was less heterogeneous, with a dominant goitrous pattern. The solid tumour already described in the RET/PTC3 models associated with cribriform patterns, suggested 'PTC spindle cell changes' as in humans PTC rather than the equivalent of the solid human PTC. Proliferation and apoptosis in the two thyroid models are related to the causal oncogene rather than reflect a general tumorigenic process. The thyroids of RET/PTC3 mice appeared as a partial and transient model of human PTCs, whereas the Tg-E7 mice do not belong to the usual PTC type.

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Haematoxylin–eosin and Cyclin D1 immunohistochemistry stainings of A and B: human differentiated thyroid carcinoma; (C and D) Human thyroid nodular goitre. Upper right inserts in A and C: small thyrocytes with high nuclear/cytoplasm ratio. Arrows in B and D: positive stromal cell nuclei for Cyclin D1. Original magnification: × 20 for A; × 60 for B; × 4 for C and × 40 for D.
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fig5: Haematoxylin–eosin and Cyclin D1 immunohistochemistry stainings of A and B: human differentiated thyroid carcinoma; (C and D) Human thyroid nodular goitre. Upper right inserts in A and C: small thyrocytes with high nuclear/cytoplasm ratio. Arrows in B and D: positive stromal cell nuclei for Cyclin D1. Original magnification: × 20 for A; × 60 for B; × 4 for C and × 40 for D.

Mentions: In the E7 model, Cyclin D1 immunolabelling was very low in follicular cells compared with WT, but was positive in the nucleus of a great number of stromal cells. It was rarely positive in control stroma (Table 3, Figure 4I and J). Some human thyroid nodular goitre and differentiated thyroid carcinoma presenting morphology and nuclear features (Figure 5A and C) similar to E7 mouse model also showed stromal cell-positive staining for Cyclin D1 (Figure 5B and D). In mouse E7 model, no apoptosis, as measured by Tunel assay and by immunohistochemical detection of activated caspase 3, could be observed in thyrocytes of both transgenic models and wild-type mice (not shown).


Human thyroid tumours, the puzzling lessons from E7 and RET/PTC3 transgenic mice.

Jin L, Burniat A, Dumont JE, Miot F, Corvilain B, Franc B - Br. J. Cancer (2008)

Haematoxylin–eosin and Cyclin D1 immunohistochemistry stainings of A and B: human differentiated thyroid carcinoma; (C and D) Human thyroid nodular goitre. Upper right inserts in A and C: small thyrocytes with high nuclear/cytoplasm ratio. Arrows in B and D: positive stromal cell nuclei for Cyclin D1. Original magnification: × 20 for A; × 60 for B; × 4 for C and × 40 for D.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2600679&req=5

fig5: Haematoxylin–eosin and Cyclin D1 immunohistochemistry stainings of A and B: human differentiated thyroid carcinoma; (C and D) Human thyroid nodular goitre. Upper right inserts in A and C: small thyrocytes with high nuclear/cytoplasm ratio. Arrows in B and D: positive stromal cell nuclei for Cyclin D1. Original magnification: × 20 for A; × 60 for B; × 4 for C and × 40 for D.
Mentions: In the E7 model, Cyclin D1 immunolabelling was very low in follicular cells compared with WT, but was positive in the nucleus of a great number of stromal cells. It was rarely positive in control stroma (Table 3, Figure 4I and J). Some human thyroid nodular goitre and differentiated thyroid carcinoma presenting morphology and nuclear features (Figure 5A and C) similar to E7 mouse model also showed stromal cell-positive staining for Cyclin D1 (Figure 5B and D). In mouse E7 model, no apoptosis, as measured by Tunel assay and by immunohistochemical detection of activated caspase 3, could be observed in thyrocytes of both transgenic models and wild-type mice (not shown).

Bottom Line: There is an 'oncogene dependent' cellular signature, maintained at all studied ages in the E7 model, less in the RET/PTC3 model.The Tg-E7 model was less heterogeneous, with a dominant goitrous pattern.The solid tumour already described in the RET/PTC3 models associated with cribriform patterns, suggested 'PTC spindle cell changes' as in humans PTC rather than the equivalent of the solid human PTC.

View Article: PubMed Central - PubMed

Affiliation: Institut de Recherche Interdisciplinaire (IRIBHM), Faculté de Médecine, Université Libre de Bruxelles (ULB), Campus Erasme, Route de Lennik 808, B 1070 Bruxelles, Belgique. lingjin@ulb.ac.be

ABSTRACT
Human rearranged RET/PTC3 (papillary thyroid carcinoma) proto-oncogene and high-risk human papillomavirus (HPV) type 16 E7 oncogene induces in the mouse a neoplastic transformation of thyroid follicular cells. We present a detailed immuno-histological study (170 mouse thyroids: RET/PTC3, E7, wild type, 2- to 10-month-old) with cell cycle proliferation and signalling pathway indicators. The characteristics of both models are different. There is an 'oncogene dependent' cellular signature, maintained at all studied ages in the E7 model, less in the RET/PTC3 model. During tumour development a large heterogeneity occurred in the Tg-RET/PTC3 model within a same tumour or within a same thyroid lobe. The Tg-E7 model was less heterogeneous, with a dominant goitrous pattern. The solid tumour already described in the RET/PTC3 models associated with cribriform patterns, suggested 'PTC spindle cell changes' as in humans PTC rather than the equivalent of the solid human PTC. Proliferation and apoptosis in the two thyroid models are related to the causal oncogene rather than reflect a general tumorigenic process. The thyroids of RET/PTC3 mice appeared as a partial and transient model of human PTCs, whereas the Tg-E7 mice do not belong to the usual PTC type.

Show MeSH
Related in: MedlinePlus