Top

Published in:

01-04-2010

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

Authors: 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

Published in: World Journal of Surgery | Issue 4/2010

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.

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

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, 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

Oskam IM, Hoebers F, Balm AJ et al (2008) Neck management in medullary thyroid carcinoma. Eur J Surg Oncol 34:71–76PubMed

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

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

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

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

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.

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.

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.

Fleming JB, Lee JE, Bouvet M et al (1999) Surgical strategy for the treatment of medullary thyroid carcinoma. Ann Surg 230:697–707CrossRefPubMed

13.

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.

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.

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.

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.

Moley JF, Fialkowski EA (2007) Evidence-based approach to the management of sporadic medullary thyroid carcinoma. World J Surg 31:946–956CrossRefPubMed

18.

Kloos RT, Eng C, Evans DB et al (2009) Medullary thyroid cancer: management guidelines of the American Thyroid Association. Thyroid 19:565–612CrossRefPubMed

19.

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.

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.

Tamagnini P, Iacobone M, Sebag F et al (2005) Lymph node involvement in macroscopic medullary thyroid carcinoma. Br J Surg 92:449–453CrossRefPubMed

22.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Machens A, Hauptmann S, Dralle H (2008) Prediction of lateral lymph node metastases in medullary thyroid cancer. Br J Surg 95:586–591CrossRefPubMed

35.

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.

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.

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.

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

Title: Tumor Protein p53-Induced Nuclear Protein (TP53INP1) Expression in Medullary Thyroid Carcinoma: A Molecular Guide to the Optimal Extent of Surgery?
Authors: 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
Publication date: 01-04-2010
Publisher: Springer-Verlag
Published in: World Journal of Surgery / Issue 4/2010
Print ISSN: 0364-2313
Electronic ISSN: 1432-2323
DOI: https://doi.org/10.1007/s00268-010-0395-6

At a glance: The STEP trials

Springer Medicine

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

Abstract

Background

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 4/2010

A Clinical Perspective on the Criteria for Liver Resection and the Use of Liver Function Tests

Validating a Simple Scoring System to Predict Malignancy and Invasiveness of Intraductal Papillary Mucinous Neoplasms of the Pancreas

Quality Control in Colorectal Cancer Care: How Many Lymph Nodes Should Be Harvested? Reply to Letter

Chronic Groin Pain After Open, Transabdominal Preperitoneal and Totally Extraperitoneal Hernia Repair

Chronic Corrosive Injuries of the Stomach—A Single Unit Experience of 109 Patients Over Thirty Years

C-Reactive Protein Is an Early Predictor of Septic Complications After Elective Colorectal Surgery