Somatostatin Receptors 2A and 5 Are Expressed in Merkel Cell Carcinoma with No Association with Disease Severity

Neuroendocrinology

Volumn 101, Issue 3, 2015, Pages 223-235

  Gardair, Charlotte ^a,b   Samimi, Mahtab ^a,b,c   Touzé, Antoine ^c   Coursaget, Pierre ^c   Lorette, Gérard ^a,b,c   Caille, Agnès ^a,b   Wierzbicka, Ewa ^e   Croué, Anne ^f   Avenel Audran, Martine ^f   Aubin, François ^g   Kerdraon, Rémy ^h   Estève, Eric ^h   Beneton, Nathalie ⁱ   Guyétant, Serge ^a,b,d  

^a UNIVERSITY HOSPITAL OF TOURS   (France)

^b Institut Technique de l'Aviculture Centre INRA Val de Loire   (France)

^c UR1282   (France)

^d Université Franaois Rabelais   (France)

^e POITIERS UNIVERSITY HOSPITAL   (France)

^f ANGERS UNIVERSITY HOSPITAL   (France)

^g UNIVERSITY HOSPITAL OF BESANÇON   (France)

^h Hospital of Orleans   (France)

ⁱ General Hospital of le Mans   (France)

Author keywords

Immunohistochemistry; Ki67 proliferative index; Merkel cell carcinoma; Outcome; Somatostatin receptor

Indexed keywords

KI 67 ANTIGEN; SOMATOSTATIN RECEPTOR; SOMATOSTATIN RECEPTOR 2A; SOMATOSTATIN RECEPTOR 5; UNCLASSIFIED DRUG; SOMATOSTATIN RECEPTOR SUBTYPE 2, HUMAN;

AGED; ARTICLE; CANCER SPECIFIC SURVIVAL; CLINICAL FEATURE; CONTROLLED STUDY; DISEASE SEVERITY; FEMALE; HUMAN; HUMAN TISSUE; IMMUNOHISTOCHEMISTRY; MAJOR CLINICAL STUDY; MALE; MERKEL CELL POLYOMAVIRUS; MERKEL CELL TUMOR; METASTASIS; OUTCOME ASSESSMENT; PRIORITY JOURNAL; PROTEIN EXPRESSION; RECURRENCE FREE SURVIVAL; SKIN TUMOR; DISEASE FREE SURVIVAL; METABOLISM; PATHOLOGY; SEVERITY OF ILLNESS INDEX; VERY ELDERLY;

AGED; AGED, 80 AND OVER; CARCINOMA, MERKEL CELL; DISEASE-FREE SURVIVAL; FEMALE; HUMANS; MALE; RECEPTORS, SOMATOSTATIN; SEVERITY OF ILLNESS INDEX; SKIN NEOPLASMS;

EID: 84931957105     PISSN: 00283835     EISSN: 14230194     Source Type: Journal    
DOI: 10.1159/000381062     Document Type: Article

References (59)

1. Rockville Merkel Cell Carcinoma Group: Merkel cell carcinoma: recent progress and current priorities on etiology, pathogenesis, and clinical management. J Clin Oncol 2009; 27: 4021-4026.
2. Feng H, Shuda M, Chang Y, Moore PS: Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science 2008; 319: 1096-1100.
3. Donepudi S, DeConti RC, Samlowski WE: Recent advances in the understanding of the genetics, etiology, and treatment of Merkel cell carcinoma. Semin Oncol 2012; 39: 163-172.
4. Miller SJ, Alam M, Andersen J, Berg D, Bichakjian CK, Bowen G, et al: Merkel cell carcinoma. J Natl Compr Canc Netw 2009; 7: 322-332.
5. Arnold R, Chen Y-J, Costa F, Falconi M, Gross D, Grossman AB, et al: ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: follow-up and documentation. Neuroendocrinology 2009; 90: 227-233.
6. Oberg K, Ferone D, Kaltsas G, Knigge U-P, Taal B, Plockinger U: ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: biotherapy. Neuroendocrinology 2009; 90: 209-213.
7. Reubi JC: Somatostatin and other peptide receptors as tools for tumor diagnosis and treatment. Neuroendocrinology 2004; 80: 51-56.
8. John M, Meyerhof W, Richter D, Waser B, Schaer JC, Scherübl H, et al: Positive somatostatin receptor scintigraphy correlates with the presence of somatostatin receptor subtype 2. Gut 1996; 38: 33-39.
9. Reubi JC, Schär JC, Waser B, Wenger S, Heppeler A, Schmitt JS, et al: Affinity profiles for human somatostatin receptor subtypes SST1-SST5 of somatostatin radiotracers selected for scintigraphic and radiotherapeutic use. Eur J Nucl Med 2000; 27: 273-282.
10. Ben-Shlomo A, Melmed S: Pasireotide-A somatostatin analog for the potential treatment of acromegaly, neuroendocrine tumors and Cushing's disease. IDrugs 2007; 10: 885-895.
11. Kim HS, Lee HS, Kim WH: Clinical significance of protein expression of cyclooxygenase-2 and somatostatin receptors in gastroenteropancreatic neuroendocrine tumors. Cancer Res Treat 2011; 43: 181-188.
12. Okuwaki K, Kida M, Mikami T, Yamauchi H, Imaizumi H, Miyazawa S, et al: Clinicopathologic characteristics of pancreatic neuroendocrine tumors and relation of somatostatin receptor type 2A to outcomes. Cancer 2013; 119: 4094-4102.
13. Corleto VD, Falconi M, Panzuto F, Milione M, De Luca O, Perri P, et al: Somatostatin receptor subtypes 2 and 5 are associated with better survival in well-differentiated endocrine carcinomas. Neuroendocrinology 2009; 89: 223-230.
14. Asnacios A, Courbon F, Rochaix P, Bauvin E, Cances-Lauwers V, Susini C, et al: Indium-111-pentetreotide scintigraphy and somatostatin receptor subtype 2 expression: new prognostic factors for malignant well-differentiated endocrine tumors. J Clin Oncol 2008; 26: 6963-6970.
15. O'Dorisio MS, Chen F, O'Dorisio TM, Wray D, Qualman SJ: Characterization of somatostatin receptors on human neuroblastoma tumors. Cell Growth Differ 1994; 5: 1-8.
16. Liu Y, Jiang L, Mu Y: Somatostatin receptor subtypes 2 and 5 are associated with better survival in operable hepatitis B-related hepatocellular carcinoma following octreotide long-acting release treatment. Oncol Lett 2013; 6: 821-828.
17. Kwekkeboom DJ, Hoff AM, Lamberts SW, Oei HY, Krenning EP: Somatostatin analogue scintigraphy. A simple and sensitive method for the in vivo visualization of Merkel cell tumors and their metastases. Arch Dermatol 1992; 128: 818-821.
18. Buder K, Lapa C, Kreissl MC, Schirbel A, Herrmann K, Schnack A, et al: Somatostatin receptor expression in Merkel cell carcinoma as target for molecular imaging. BMC Cancer 2014; 14: 268.
19. Durani BK, Klein A, Henze M, Haberkorn U, Hartschuh W: Somatostatin analogue scintigraphy in Merkel cell tumours. Br J Dermatol 2003; 148: 1135-1140.
20. Guitera-Rovel P, Lumbroso J, Gautier-Gougis MS, Spatz A, Mercier S, Margulis A, et al: Indium-111 octreotide scintigraphy of Merkel cell carcinomas and their metastases. Ann Oncol 2001; 12: 807-811.
21. Lu Y, Fleming SE, Fields RC, Coit DG, Carrasquillo JA: Comparison of 18F-FDG PET/ CT and 111In pentetreotide scan for detection of Merkel cell carcinoma. Clin Nucl Med 2012; 37: 759-762.
22. Epstude M, Tornquist K, Riklin C, di Lenardo F, Winterhalder R, Hug U, et al: Comparison of 18 F-FDG PET/CT and 68 Ga-DOTATATE PET/CT imaging in metastasized Merkel cell carcinoma. Clin Nucl Med 2013; 38: 283-284.
23. Fakiha M, Letertre P, Vuillez JP, Lebeau J: Remission of Merkel cell tumor after somatostatin analog treatment. J Cancer Res Ther 2010; 6: 382-384.
24. Cirillo F, Filippini L, Lima GF, Caresana G, Alquati P: Merkel cell tumor. Report of case and treatment with octreotide (in Italian). Minerva Chir 1997; 52: 1359-1365.
25. Cirillo F, Vismarra M, Cafaro I, Martinotti M: Merkel cell carcinoma: A retrospective study on 48 cases and review of literature. J Oncol 2012; 2012: 749030.
26. Meier G, Waldherr C, Herrmann R, Maecke H, Mueller-Brand J, Pless M: Successful targeted radiotherapy with 90 Y-DOTATOC in a patient with Merkel cell carcinoma. Oncology 2004; 66: 160-163.
27. Salavati A, Prasad V, Schneider C-P, Herbst R, Baum RP: Peptide receptor radionuclide therapy of Merkel cell carcinoma using 177 lutetium-labeled somatostatin analogs in combination with radiosensitizing chemotherapy: A potential novel treatment based on molecular pathology. Ann Nucl Med 2012; 26: 365-369.
28. Schmidt MC, Uhrhan K, Markiefka B, Hasselbring L, Schlaak M, Cremer B, et al: 68 Ga-DotaTATE PET-CT followed by peptide receptor radiotherapy in combination with capecitabine in two patients with Merkel cell carcinoma. Int J Clin Exp Med 2012; 5: 363.
29. Papotti M, Macri L, Pagani A, Aloi F, Bussolati G: Quantitation of somatostatin receptor type 2 in neuroendocrine Merkel cell carcinoma of the skin by competitive RT-PCR. Endocr Pathol 1999; 10: 37-46.
30. Touzé A, Le Bidre E, Laude H, Fleury MJJ, Cazal R, Arnold F, et al: High levels of antibodies against Merkel cell polyomavirus identify a subset of patients with Merkel cell carcinoma with better clinical outcome. J Clin Oncol 2011; 29: 1612-1619.
31. Samimi M, Touzé A, Laude H, Le Bidre E, Arnold F, Carpentier A, et al: Vitamin D deficiency is associated with greater tumor size and poorer outcome in Merkel cell carcinoma patients. J Eur Acad Dermatol Venereol 2014; 28: 298-308.
32. Fischer T, Doll C, Jacobs S, Kolodziej A, Stumm R, Schulz S: Reassessment of sst 2 somatostatin receptor expression in human normal and neoplastic tissues using the novel rabbit monoclonal antibody UMB-1. J Clin Endocrinol Metab 2008; 93: 4519-4524.
33. Lupp A, Hunder A, Petrich A, Nagel F, Doll C, Schulz S: Reassessment of sst 5 somatostatin receptor expression in normal and neoplastic human tissues using the novel rabbit monoclonal antibody UMB-4. Neuroendocrinology 2011; 94: 255-264.
34. Kaemmerer D, Lupp A, Peter L, Fischer E, Schulz S, Klöppel G, et al: Correlation of monoclonal and polyclonal somatostatin receptor 5 antibodies in pancreatic neuroendocrine tumors. Int J Clin Exp Pathol 2013; 6: 49-54.
35. Hagströmer L, Emtestam L, Stridsberg M, Talme T: Expression pattern of somatostatin receptor subtypes 1-5 in human skin: an immunohistochemical study of healthy subjects and patients with psoriasis or atopic dermatitis. Exp Dermatol 2006; 15: 950-957.
36. Vockel M, Breitenbach U, Kreienkamp H-J, Brandner JM: Somatostatin regulates tight junction function and composition in human keratinocytes: somatostatin and tight junctions in keratinocytes. Exp Dermatol 2010; 19: 888-894.
37. Fantini F, Johansson O: Neurochemical markers in human cutaneous Merkel cells. An immunohistochemical investigation. Exp Dermatol 1995; 4: 365-371.
38. Tilling T, Moll I: Which are the cells of origin in Merkel cell carcinoma? J Skin Cancer 2012; 2012: 1-6.
39. Shuda M, Arora R, Kwun HJ, Feng H, Sarid R, Fernández-Figueras MT, et al: Human Merkel cell polyomavirus infection I. MCV T antigen expression in Merkel cell carcinoma, lymphoid tissues and lymphoid tumors. Int J Cancer 2009; 125: 1243-1249.
40. Nakamura T, Sato Y, Watanabe D, Ito H, Shimonohara N, Tsuji T, et al: Nuclear localization of Merkel cell polyomavirus large T antigen in Merkel cell carcinoma. Virology 2010; 398: 273-279.
41. Erovic BM, Al Habeeb A, Harris L, Goldstein DP, Ghazarian D, Irish JC: Significant overexpression of the Merkel cell polyomavirus (MCPyV) large T antigen in Merkel cell carcinoma. Head Neck 2013; 35: 184-189.
42. Rodig SJ, Cheng J, Wardzala J, DoRosario A, Scanlon JJ, Laga AC, et al: Improved detection suggests all Merkel cell carcinomas harbor Merkel polyomavirus. J Clin Invest 2012; 122: 4645-4653.
43. Harms PW, Patel RM, Verhaegen ME, Giordano TJ, Nash KT, Johnson CN, et al: Distinct gene expression profiles of viral-and nonviral-associated Merkel cell carcinoma revealed by transcriptome analysis. J Invest Dermatol 2013; 133: 936-945.
44. Bhatia K, Goedert JJ, Modali R, Preiss L, Ayers LW: Immunological detection of viral large T antigen identifies a subset of Merkel cell carcinoma tumors with higher viral abundance and better clinical outcome. Int J Cancer 2010; 127: 1493-1496.
45. Sihto H, Kukko H, Koljonen V, Sankila R, Böhling T, Joensuu H: Merkel cell polyomavirus infection, large T antigen, retinoblastoma protein and outcome in Merkel cell carcinoma. Clin Cancer Res 2011; 17: 4806-4813.
46. Kuwamoto S, Higaki H, Kanai K, Iwasakia T, Sano H, Nagata K, et al: Association of Merkel cell polyomavirus infection with morphologic differences in Merkel cell carcinoma. Hum Pathol 2011; 42: 632-640.
47. Higaki-Mori H, Kuwamoto S, Iwasaki T, Kato M, Murakami I, Nagata K, et al: Association of Merkel cell polyomavirus infection with clinicopathological differences in Merkel cell carcinoma. Hum Pathol 2012; 43: 2282-2291.
48. Tucci MG, Lucarini G, Giangiacomi M, Zizzi A, Criante P, Ricotti G, et al: Immunohistochemical study of apoptosis markers and involvement of chemokine CXCR4 in skin Merkel cell carcinoma. J Eur Acad Dermatol Venereol 2006; 20: 1220-1225.
49. Llombart B, Monteagudo C, López-Guerrero JA, Carda C, Jorda E, Sanmartín O, et al: Clinicopathological and immunohistochemical analysis of 20 cases of Merkel cell carcinoma in search of prognostic markers. Histopathology 2005; 46: 622-634.
50. Fernández-Figueras MT, Puig L, Musulen E, Gilaberte M, Ferrándiz C, Lerma E, et al: Prognostic significance of p27Kip1, p45Skp2 and Ki67 expression profiles in Merkel cell carcinoma, extracutaneous small cell carcinoma, and cutaneous squamous cell carcinoma. Histopathology 2005; 46: 614-621.
51. Vujic I, Marker M, Posch C, Muhlehner D, Monshi B, Breier F, et al: Merkel cell carcinoma: mitoses, expression of Ki-67 and bcl-2 correlate with disease progression. J Eur Acad Dermatol Venereol 2015; 29: 542-548.
52. Koljonen V, Tukiainen E, Haglund C, Böhling T: Proliferative activity detected by Ki67 correlates with poor outcome in Merkel cell carcinoma. Histopathology 2006; 49: 551-553.
53. Kloppel G, Couvelard A, Perren A, Komminoth P, McNicol AM, Nilsson O, et al: ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: towards a standardized approach to the diagnosis of gastroenteropancreatic neuroendocrine tumors and their prognostic stratification. Neuroendocrinology 2009; 90: 162-166.
54. Buchmann I, Henze M, Engelbrecht S, Eisenhut M, Runz A, Schäfer M, et al: Comparison of 68 Ga-DOTATOC PET and 111 In-DTPAOC (Octreoscan) SPECT in patients with neuroendocrine tumours. Eur J Nucl Med Mol Imaging 2007; 34: 1617-1626.
55. Körner M, Waser B, Schonbrunn A, Perren A, Reubi JC: Somatostatin receptor subtype 2A immunohistochemistry using a new monoclonal antibody selects tumors suitable for in vivo somatostatin receptor targeting. Am J Surg Pathol 2012; 36: 242-252.
56. Kaemmerer D, Peter L, Lupp A, Schulz S, Sänger J, Prasad V, et al: Molecular imaging with 68 Ga-SSTR PET/CT and correlation to immunohistochemistry of somatostatin receptors in neuroendocrine tumours. Eur J Nucl Med Mol Imaging 2011; 38: 1659-1668.
57. Müssig K, ?ksüz MO, Dudziak K, Ueberberg B, Wehrmann M, Horger M, et al: Association of somatostatin receptor 2 immunohistochemical expression with [ 111 In]-DTPA octreotide scintigraphy and [ 68 Ga]-DOTATOC PET/CT in neuroendocrine tumors. Horm Metab Res 2010; 42: 599-606.
58. Fougner SL, Borota OC, Berg JP, Hald JK, Ramm-Pettersen J, Bollerslev J: The clinical response to somatostatin analogues in acromegaly correlates to the somatostatin receptor subtype 2a protein expression of the adenoma. Clin Endocrinol 2008; 68: 458-465.
59. Casar-Borota O, Heck A, Schulz S, Nesland JM, Ramm-Pettersen J, Lekva T, et al: Expression of SSTR2a, but not of SSTRs 1, 3, or 5 in somatotroph adenomas assessed by monoclonal antibodies was reduced by octreotide and correlated with the acute and long-term effects of octreotide. J Clin Endocrinol Metab 2013; 98: 1730-1739.