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Erschienen in: World Journal of Surgery 4/2010

01.04.2010

Tumor Protein p53-Induced Nuclear Protein (TP53INP1) Expression in Medullary Thyroid Carcinoma: A Molecular Guide to the Optimal Extent of Surgery?

verfasst von: D. Taïeb, S. Giusiano, F. Sebag, M. Marcy, C. de Micco, F. F. Palazzo, N. J. Dusetti, J. L. Iovanna, J. F. Henry, S. Garcia, Colette Taranger-Charpin

Erschienen in: World Journal of Surgery | Ausgabe 4/2010

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Abstract

Background

Medullary thyroid cancer (MTC) is characterized by early regional lymph node metastasis, the presence of which represents a critical obstacle to cure. At present no molecular markers have been successfully integrated into the clinical care of sporadic MTC. The present study was designed to evaluate TP53INP1 expression in MTC and to assess its ability to guide the surgeon to the optimal extent of surgery performed with curative intent.

Methods

Thirty-eight patients with sporadic MTC were evaluated. TP53INP1 immunoexpression was studied on embedded paraffin material and on cytological smears.

Results

TP53INP1 was expressed in normal C cells, in C-cell hyperplasia, and in 57.9% of MTC. It was possible to identify two groups of MTC according to the proportion of TP53INP1 expressing tumor cells: group 1 from 0% to <50% and group 2 from 50% to 100% of positive cells. Patients with a decreased expression of TP53INP1 (group 1) had a lower rate of nodal metastasis (18.8% versus 63.4% in group 2; P = 0.009), with only minimal lymph node involvement per N1 patient (2.7% of positive lymph nodes versus 22.9%; P < 0.001) and better outcomes (100% of biochemical cure versus 55.5%; P < 0.001). Patients with distant metastases were only observed in group 2. Cytological samples exhibit similar results to their embedded counterparts.

Conclusions

TP53INP1 immunoexpression appears to be a clinical predictor of lymph node metastasis in MTC. The evaluation of TP53INP1 expression may guide the extent of lymph node dissection in the clinically node-negative neck. These findings require prospective validation.
Literatur
1.
Zurück zum Zitat Dralle H, Scheumann GF, Proye C et al (1995) The value of lymph node dissection in hereditary medullary thyroid carcinoma: a retrospective, European, multicentre study. J Intern Med 238:357–361CrossRefPubMed Dralle H, Scheumann GF, Proye C et al (1995) The value of lymph node dissection in hereditary medullary thyroid carcinoma: a retrospective, European, multicentre study. J Intern Med 238:357–361CrossRefPubMed
2.
Zurück zum Zitat Machens A, Hinze R, Thomusch O et al (2002) Pattern of nodal metastasis for primary and reoperative thyroid cancer. World J Surg 26:22–28CrossRefPubMed Machens A, Hinze R, Thomusch O et al (2002) Pattern of nodal metastasis for primary and reoperative thyroid cancer. World J Surg 26:22–28CrossRefPubMed
3.
Zurück zum Zitat Machens A, Hofmann C, Hauptmann S et al (2007) Locoregional recurrence and death from medullary thyroid carcinoma in a contemporaneous series: 5-year results. Eur J Endocrinol 157:85–93CrossRefPubMed Machens A, Hofmann C, Hauptmann S et al (2007) Locoregional recurrence and death from medullary thyroid carcinoma in a contemporaneous series: 5-year results. Eur J Endocrinol 157:85–93CrossRefPubMed
4.
Zurück zum Zitat Oskam IM, Hoebers F, Balm AJ et al (2008) Neck management in medullary thyroid carcinoma. Eur J Surg Oncol 34:71–76PubMed Oskam IM, Hoebers F, Balm AJ et al (2008) Neck management in medullary thyroid carcinoma. Eur J Surg Oncol 34:71–76PubMed
5.
Zurück zum Zitat Hundahl SA, Fleming ID, Fremgen AM et al (1998) A National Cancer Data Base report on 53, 856 cases of thyroid carcinoma treated in the U.S., 1985–1995 (see Comments). Cancer 83:2638–2648CrossRefPubMed Hundahl SA, Fleming ID, Fremgen AM et al (1998) A National Cancer Data Base report on 53, 856 cases of thyroid carcinoma treated in the U.S., 1985–1995 (see Comments). Cancer 83:2638–2648CrossRefPubMed
6.
Zurück zum Zitat Modigliani E, Cohen R, Campos JM et al (1998) Prognostic factors for survival and for biochemical cure in medullary thyroid carcinoma: results in 899 patients. The GETC Study Group. Groupe d’etude des tumeurs a calcitonine. Clin Endocrinol (Oxf) 48:265–273CrossRef Modigliani E, Cohen R, Campos JM et al (1998) Prognostic factors for survival and for biochemical cure in medullary thyroid carcinoma: results in 899 patients. The GETC Study Group. Groupe d’etude des tumeurs a calcitonine. Clin Endocrinol (Oxf) 48:265–273CrossRef
7.
Zurück zum Zitat Raue F, Kotzerke J, Reinwein D et al (1993) Prognostic factors in medullary thyroid carcinoma: evaluation of 741 patients from the German Medullary Thyroid Carcinoma Register. Clin Invest 71:7–12CrossRef Raue F, Kotzerke J, Reinwein D et al (1993) Prognostic factors in medullary thyroid carcinoma: evaluation of 741 patients from the German Medullary Thyroid Carcinoma Register. Clin Invest 71:7–12CrossRef
8.
Zurück zum Zitat Machens A, Gimm O, Ukkat J et al (2000) Improved prediction of calcitonin normalization in medullary thyroid carcinoma patients by quantitative lymph node analysis. Cancer 88:1909–1915CrossRefPubMed Machens A, Gimm O, Ukkat J et al (2000) Improved prediction of calcitonin normalization in medullary thyroid carcinoma patients by quantitative lymph node analysis. Cancer 88:1909–1915CrossRefPubMed
9.
Zurück zum Zitat Scollo C, Baudin E, Travagli JP et al (2003) Rationale for central and bilateral lymph node dissection in sporadic and hereditary medullary thyroid cancer. J Clin Endocrinol Metab 88:2070–2075CrossRefPubMed Scollo C, Baudin E, Travagli JP et al (2003) Rationale for central and bilateral lymph node dissection in sporadic and hereditary medullary thyroid cancer. J Clin Endocrinol Metab 88:2070–2075CrossRefPubMed
10.
Zurück zum Zitat Weber T, Schilling T, Frank-Raue K et al (2001) Impact of modified radical neck dissection on biochemical cure in medullary thyroid carcinomas. Surgery 130:1044–1049CrossRefPubMed Weber T, Schilling T, Frank-Raue K et al (2001) Impact of modified radical neck dissection on biochemical cure in medullary thyroid carcinomas. Surgery 130:1044–1049CrossRefPubMed
11.
Zurück zum Zitat Ellenhorn JD, Shah JP, Brennan MF (1993) Impact of therapeutic regional lymph node dissection for medullary carcinoma of the thyroid gland. Surgery 114:1078–1081 (discussion 1081–1072)PubMed Ellenhorn JD, Shah JP, Brennan MF (1993) Impact of therapeutic regional lymph node dissection for medullary carcinoma of the thyroid gland. Surgery 114:1078–1081 (discussion 1081–1072)PubMed
12.
Zurück zum Zitat Fleming JB, Lee JE, Bouvet M et al (1999) Surgical strategy for the treatment of medullary thyroid carcinoma. Ann Surg 230:697–707CrossRefPubMed Fleming JB, Lee JE, Bouvet M et al (1999) Surgical strategy for the treatment of medullary thyroid carcinoma. Ann Surg 230:697–707CrossRefPubMed
13.
Zurück zum Zitat Kallinowski F, Buhr HJ, Meybier H et al (1993) Medullary carcinoma of the thyroid—therapeutic strategy derived from fifteen years of experience. Surgery 114:491–496PubMed Kallinowski F, Buhr HJ, Meybier H et al (1993) Medullary carcinoma of the thyroid—therapeutic strategy derived from fifteen years of experience. Surgery 114:491–496PubMed
14.
Zurück zum Zitat Kebebew E, Kikuchi S, Duh QY et al (2000) Long-term results of reoperation and localizing studies in patients with persistent or recurrent medullary thyroid cancer. Arch Surg 135:895–901CrossRefPubMed Kebebew E, Kikuchi S, Duh QY et al (2000) Long-term results of reoperation and localizing studies in patients with persistent or recurrent medullary thyroid cancer. Arch Surg 135:895–901CrossRefPubMed
15.
Zurück zum Zitat Machens A, Holzhausen HJ, Dralle H (2006) Contralateral cervical and mediastinal lymph node metastasis in medullary thyroid cancer: systemic disease? Surgery 139:28–32CrossRefPubMed Machens A, Holzhausen HJ, Dralle H (2006) Contralateral cervical and mediastinal lymph node metastasis in medullary thyroid cancer: systemic disease? Surgery 139:28–32CrossRefPubMed
16.
Zurück zum Zitat Moley JF, DeBenedetti MK (1999) Patterns of nodal metastases in palpable medullary thyroid carcinoma: recommendations for extent of node dissection. Ann Surg 229:880–887 (discussion 887–888)CrossRefPubMed Moley JF, DeBenedetti MK (1999) Patterns of nodal metastases in palpable medullary thyroid carcinoma: recommendations for extent of node dissection. Ann Surg 229:880–887 (discussion 887–888)CrossRefPubMed
17.
Zurück zum Zitat Moley JF, Fialkowski EA (2007) Evidence-based approach to the management of sporadic medullary thyroid carcinoma. World J Surg 31:946–956CrossRefPubMed Moley JF, Fialkowski EA (2007) Evidence-based approach to the management of sporadic medullary thyroid carcinoma. World J Surg 31:946–956CrossRefPubMed
18.
Zurück zum Zitat Kloos RT, Eng C, Evans DB et al (2009) Medullary thyroid cancer: management guidelines of the American Thyroid Association. Thyroid 19:565–612CrossRefPubMed Kloos RT, Eng C, Evans DB et al (2009) Medullary thyroid cancer: management guidelines of the American Thyroid Association. Thyroid 19:565–612CrossRefPubMed
19.
Zurück zum Zitat Iacobone M, Niccoli-Sire P, Sebag F et al (2002) Can sporadic medullary thyroid carcinoma be biochemically predicted? Prospective analysis of 66 operated patients with elevated serum calcitonin levels. World J Surg 26:886–890CrossRefPubMed Iacobone M, Niccoli-Sire P, Sebag F et al (2002) Can sporadic medullary thyroid carcinoma be biochemically predicted? Prospective analysis of 66 operated patients with elevated serum calcitonin levels. World J Surg 26:886–890CrossRefPubMed
20.
Zurück zum Zitat Niccoli-Sire P, Murat A, Rohmer V et al (2003) When should thyroidectomy be performed in familial medullary thyroid carcinoma gene carriers with non-cysteine RET mutations? Surgery 134:1029–1036 (discussion 1036–1027)CrossRefPubMed Niccoli-Sire P, Murat A, Rohmer V et al (2003) When should thyroidectomy be performed in familial medullary thyroid carcinoma gene carriers with non-cysteine RET mutations? Surgery 134:1029–1036 (discussion 1036–1027)CrossRefPubMed
21.
Zurück zum Zitat Tamagnini P, Iacobone M, Sebag F et al (2005) Lymph node involvement in macroscopic medullary thyroid carcinoma. Br J Surg 92:449–453CrossRefPubMed Tamagnini P, Iacobone M, Sebag F et al (2005) Lymph node involvement in macroscopic medullary thyroid carcinoma. Br J Surg 92:449–453CrossRefPubMed
22.
Zurück zum Zitat Koperek O, Scheuba C, Cherenko M et al (2008) Desmoplasia in medullary thyroid carcinoma: a reliable indicator of metastatic potential. Histopathology 52:623–630CrossRefPubMed Koperek O, Scheuba C, Cherenko M et al (2008) Desmoplasia in medullary thyroid carcinoma: a reliable indicator of metastatic potential. Histopathology 52:623–630CrossRefPubMed
23.
Zurück zum Zitat Machens A, Holzhausen HJ, Lautenschlager C et al (2003) Enhancement of lymph node metastasis and distant metastasis of thyroid carcinoma Cancer 98:712–719 Machens A, Holzhausen HJ, Lautenschlager C et al (2003) Enhancement of lymph node metastasis and distant metastasis of thyroid carcinoma Cancer 98:712–719
24.
Zurück zum Zitat Scheuba C, Kaserer K, Kaczirek K et al (2006) Desmoplastic stromal reaction in medullary thyroid cancer—an intraoperative “marker” for lymph node metastases. World J Surg 30:853–859CrossRefPubMed Scheuba C, Kaserer K, Kaczirek K et al (2006) Desmoplastic stromal reaction in medullary thyroid cancer—an intraoperative “marker” for lymph node metastases. World J Surg 30:853–859CrossRefPubMed
25.
Zurück zum Zitat Gironella M, Seux M, Xie MJ et al (2007) Tumor protein 53-induced nuclear protein 1 expression is repressed by miR-155, and its restoration inhibits pancreatic tumor development. Proc Natl Acad Sci USA 104:16170–16175CrossRefPubMed Gironella M, Seux M, Xie MJ et al (2007) Tumor protein 53-induced nuclear protein 1 expression is repressed by miR-155, and its restoration inhibits pancreatic tumor development. Proc Natl Acad Sci USA 104:16170–16175CrossRefPubMed
26.
Zurück zum Zitat Tomasini R, Samir AA, Carrier A et al (2003) TP53INP1s and homeodomain-interacting protein kinase-2 (HIPK2) are partners in regulating p53 activity. J Biol Chem 278:37722–37729CrossRefPubMed Tomasini R, Samir AA, Carrier A et al (2003) TP53INP1s and homeodomain-interacting protein kinase-2 (HIPK2) are partners in regulating p53 activity. J Biol Chem 278:37722–37729CrossRefPubMed
27.
Zurück zum Zitat Tomasini R, Samir AA, Pebusque MJ et al (2002) P53-dependent expression of the stress-induced protein (SIP). Eur J Cell Biol 81:294–301CrossRefPubMed Tomasini R, Samir AA, Pebusque MJ et al (2002) P53-dependent expression of the stress-induced protein (SIP). Eur J Cell Biol 81:294–301CrossRefPubMed
28.
Zurück zum Zitat Tomasini R, Seux M, Nowak J et al (2005) TP53INP1 is a novel p73 target gene that induces cell cycle arrest and cell death by modulating p73 transcriptional activity. Oncogene 24:8093–8104PubMed Tomasini R, Seux M, Nowak J et al (2005) TP53INP1 is a novel p73 target gene that induces cell cycle arrest and cell death by modulating p73 transcriptional activity. Oncogene 24:8093–8104PubMed
29.
Zurück zum Zitat Herfarth KK, Wick MR, Marshall HN et al (1997) Absence of TP53 alterations in pheochromocytomas and medullary thyroid carcinomas. Genes Chromosom Cancer 20:24–29CrossRefPubMed Herfarth KK, Wick MR, Marshall HN et al (1997) Absence of TP53 alterations in pheochromocytomas and medullary thyroid carcinomas. Genes Chromosom Cancer 20:24–29CrossRefPubMed
30.
Zurück zum Zitat Chevrier L, Meunier AC, Cochaud S et al (2008) Vasoactive intestinal peptide decreases MYCN expression and synergizes with retinoic acid in a human MYCN-amplified neuroblastoma cell line. Int J Oncol 33:1081–1089PubMed Chevrier L, Meunier AC, Cochaud S et al (2008) Vasoactive intestinal peptide decreases MYCN expression and synergizes with retinoic acid in a human MYCN-amplified neuroblastoma cell line. Int J Oncol 33:1081–1089PubMed
31.
Zurück zum Zitat Gommeaux J, Cano C, Garcia S et al (2007) Colitis and colitis-associated cancer are exacerbated in mice deficient for tumor protein 53-induced nuclear protein 1. Mol Cell Biol 27:2215–2228CrossRefPubMed Gommeaux J, Cano C, Garcia S et al (2007) Colitis and colitis-associated cancer are exacerbated in mice deficient for tumor protein 53-induced nuclear protein 1. Mol Cell Biol 27:2215–2228CrossRefPubMed
32.
Zurück zum Zitat Jiang PH, Motoo Y, Garcia S et al (2006) Down-expression of tumor protein p53-induced nuclear protein 1 in human gastric cancer. World J Gastroenterol 12:691–696PubMed Jiang PH, Motoo Y, Garcia S et al (2006) Down-expression of tumor protein p53-induced nuclear protein 1 in human gastric cancer. World J Gastroenterol 12:691–696PubMed
33.
Zurück zum Zitat Jiang PH, Motoo Y, Sawabu N et al (2006) Effect of gemcitabine on the expression of apoptosis-related genes in human pancreatic cancer cells. World J Gastroenterol 12:1597–1602PubMed Jiang PH, Motoo Y, Sawabu N et al (2006) Effect of gemcitabine on the expression of apoptosis-related genes in human pancreatic cancer cells. World J Gastroenterol 12:1597–1602PubMed
34.
Zurück zum Zitat Machens A, Hauptmann S, Dralle H (2008) Prediction of lateral lymph node metastases in medullary thyroid cancer. Br J Surg 95:586–591CrossRefPubMed Machens A, Hauptmann S, Dralle H (2008) Prediction of lateral lymph node metastases in medullary thyroid cancer. Br J Surg 95:586–591CrossRefPubMed
35.
Zurück zum Zitat Jiang PH, Motoo Y, Iovanna JL et al (2004) Tumor protein p53-induced nuclear protein 1 (TP53INP1) in spontaneous chronic pancreatitis in the WBN/Kob rat: drug effects on its expression in the pancreas. JOP 5:205–216PubMed Jiang PH, Motoo Y, Iovanna JL et al (2004) Tumor protein p53-induced nuclear protein 1 (TP53INP1) in spontaneous chronic pancreatitis in the WBN/Kob rat: drug effects on its expression in the pancreas. JOP 5:205–216PubMed
36.
Zurück zum Zitat Ito Y, Motoo Y, Yoshida H et al (2006) Decreased expression of tumor protein p53-induced nuclear protein 1 (TP53INP1) in breast carcinoma. Anticancer Res 26:4391–4395PubMed Ito Y, Motoo Y, Yoshida H et al (2006) Decreased expression of tumor protein p53-induced nuclear protein 1 (TP53INP1) in breast carcinoma. Anticancer Res 26:4391–4395PubMed
37.
Zurück zum Zitat Ito Y, Motoo Y, Yoshida H et al (2006) High level of tumour protein p53-induced nuclear protein 1 (TP53INP1) expression in anaplastic carcinoma of the thyroid. Pathology 38:545–547CrossRefPubMed Ito Y, Motoo Y, Yoshida H et al (2006) High level of tumour protein p53-induced nuclear protein 1 (TP53INP1) expression in anaplastic carcinoma of the thyroid. Pathology 38:545–547CrossRefPubMed
38.
Zurück zum Zitat Nikiforova MN, Tseng GC, Steward D et al (2008) MicroRNA expression profiling of thyroid tumors: biological significance and diagnostic utility. J Clin Endocrinol Metab 93:1600–1608CrossRefPubMed Nikiforova MN, Tseng GC, Steward D et al (2008) MicroRNA expression profiling of thyroid tumors: biological significance and diagnostic utility. J Clin Endocrinol Metab 93:1600–1608CrossRefPubMed
Metadaten
Titel
Tumor Protein p53-Induced Nuclear Protein (TP53INP1) Expression in Medullary Thyroid Carcinoma: A Molecular Guide to the Optimal Extent of Surgery?
verfasst von
D. Taïeb
S. Giusiano
F. Sebag
M. Marcy
C. de Micco
F. F. Palazzo
N. J. Dusetti
J. L. Iovanna
J. F. Henry
S. Garcia
Colette Taranger-Charpin
Publikationsdatum
01.04.2010
Verlag
Springer-Verlag
Erschienen in
World Journal of Surgery / Ausgabe 4/2010
Print ISSN: 0364-2313
Elektronische ISSN: 1432-2323
DOI
https://doi.org/10.1007/s00268-010-0395-6

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