Prognostic value of MIB-1 proliferation index in solitary fibrous tumors of the pleura implemented in a new score - a multicenter study

Matthias Diebold, Alex Soltermann, Selma Hottinger, Sarah R Haile, Lukas Bubendorf, Paul Komminoth, Wolfram Jochum, Rainer Grobholz, Dirk Theegarten, Sabina Berezowska, Kaid Darwiche, Filiz Oezkan, Malcolm Kohler, Daniel P Franzen, Matthias Diebold, Alex Soltermann, Selma Hottinger, Sarah R Haile, Lukas Bubendorf, Paul Komminoth, Wolfram Jochum, Rainer Grobholz, Dirk Theegarten, Sabina Berezowska, Kaid Darwiche, Filiz Oezkan, Malcolm Kohler, Daniel P Franzen

Abstract

Background: Although the majority of solitary fibrous tumors of the pleura (SFTP) follow a benign course, 10-25% of patients suffer from recurrence or metastatic disease. Several scoring models have been proposed to predict the outcome. However, none of these included immunohistochemical (IHC) markers as possible prognosticators.

Methods: In this multicenter study, we collected clinical data and formalin-fixed and paraffin-embedded (FFPE) tissue blocks of patients with histologically proven SFTP which had been surgically resected between 2000 und 2015. After systematic and extensive IHC staining on tissue microarrays, the results were analyzed and compared to histomorphological and clinical data for their possible prognostic value.

Results: In total, 78 patients (mean age 61 ± 11 years) were included. Of these, 9 patients (11%) had an adverse outcome including SFTP recurrence (n = 6) or SFTP-related death (n = 3). Mean overall survival was 172 ± 13 months. 1 and 10-year event-free survival rates were 99% and 93%. In the multivariable analysis only MIB-1 proliferation index (Ki-67) ≥10% (HR 12.3, CI 1.1-139.5, p = 0.043), ≥4 mitoses per 10 high power fields (HR 36.5, CI 1.2-1103.7, p = 0.039) and tumor size larger than 10 cm (HR 81.8, CI 1.7-4016.8, p = 0.027) were independently associated with adverse outcome.

Conclusion: A high proliferation rate by MIB-1 IHC was associated with impaired outcome. Upon this, we established a new score using mitosis, necrosis, size of the tumor and MIB-1, which performed better than the traditional scores in our data set. This prognostic score could help to better evaluate outcome of SFTP, but requires external validation.

Trial registration: ClinicalTrials.gov NCT01694654.

Keywords: MIB-1 proliferation index; Outcome; Pleura; Score; Solitary fibrous tumor.

Conflict of interest statement

Ethics approval and consent to participate

Written informed consent was obtained from all patients or their relatives. The study was approved by the Ethics committee of the Canton of Zurich (KEK-ZH 2012–0279), and the study was notified at Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Study flowchart. SFT(P), solitary fibrous tumor (of the pleura)
Fig. 2
Fig. 2
Kaplan-Meier survival curve according to MIB-1 proliferation index (Ki-67)
Fig. 3
Fig. 3
Kaplan-Meier survival curve according the new scoring system

References

    1. Chick JF, Chauhan NR, Madan R. Solitary fibrous tumors of the thorax: nomenclature, epidemiology, radiologic and pathologic findings, differential diagnoses, and management. AJR Am J Roentgenol. 2013;200:W238–W248. doi: 10.2214/AJR.11.8430.
    1. Briselli M, Mark EJ, Dickersin GR. Solitary fibrous tumors of the pleura: eight new cases and review of 360 cases in the literature. Cancer. 1981;47:2678–2689. doi: 10.1002/1097-0142(19810601)47:11<2678::AID-CNCR2820471126>;2-9.
    1. Okike N, Bernatz PE, Woolner LB. Localized mesothelioma of the pleura: benign and malignant variants. J Thorac Cardiovasc Surg. 1978;75:363–372.
    1. Zhanlong M, Haibin S, Xiangshan F, Jiacheng S, Yicheng N. Variable solitary fibrous tumor locations: CT and MR imaging features. Medicine (Baltimore) 2016;95:e3031. doi: 10.1097/MD.0000000000003031.
    1. Gengler C, Guillou L. Solitary fibrous tumour and haemangiopericytoma: evolution of a concept. Histopathology. 2006;48:63–74. doi: 10.1111/j.1365-2559.2005.02290.x.
    1. Klemperer P, Coleman BR. Primary neoplasms of the pleura. A report of five cases. Am J Ind Med. 1992;22:1–31. doi: 10.1002/ajim.4700220103.
    1. Stout AP, Murray MR. Hemangiopericytoma: A vascular tumor featuring zimmermann's pericytes. Ann Surg. 1942;116:26–33. doi: 10.1097/00000658-194207000-00004.
    1. el-Naggar AK, Ro JY, Ayala AG, Ward R, Ordóñez NG. Localized fibrous tumor of the serosal cavities. Immunohistochemical, electron-microscopic, and flow-cytometric DNA study. Am J Clin Pathol. 1989;92:561–565. doi: 10.1093/ajcp/92.5.561.
    1. Flint A, Weiss SW. CD-34 and keratin expression distinguishes solitary fibrous tumor (fibrous mesothelioma) of pleura from desmoplastic mesothelioma. Hum Pathol. 1995;26:428–431. doi: 10.1016/0046-8177(95)90145-0.
    1. Chmielecki J, Crago AM, Rosenberg M, O'Connor R, Walker SR, Ambrogio L, Auclair D, McKenna A, Heinrich MC, Frank DA, Meyerson M. Whole-exome sequencing identifies a recurrent NAB2-STAT6 fusion in solitary fibrous tumors. Nat Genet. 2013;45:131–132. doi: 10.1038/ng.2522.
    1. Robinson DR, Wu YM, Kalyana-Sundaram S, Cao X, Lonigro RJ, Sung YS, Chen CL, Zhang L, Wang R, Su F, et al. Identification of recurrent NAB2-STAT6 gene fusions in solitary fibrous tumor by integrative sequencing. Nat Genet. 2013;45:180–185. doi: 10.1038/ng.2509.
    1. Doyle LA, Vivero M, Fletcher CD, Mertens F, Hornick JL. Nuclear expression of STAT6 distinguishes solitary fibrous tumor from histologic mimics. Mod Pathol. 2014;27:390–395. doi: 10.1038/modpathol.2013.247.
    1. Tai HC, Chuang IC, Chen TC, Li CF, Huang SC, Kao YC, Lin PC, Tsai JW, Lan J, Yu SC, et al. NAB2-STAT6 fusion types account for clinicopathological variations in solitary fibrous tumors. Mod Pathol. 2015;28:1324–1335. doi: 10.1038/modpathol.2015.90.
    1. Barthelmeß S, Geddert H, Boltze C, Moskalev EA, Bieg M, Sirbu H, Brors B, Wiemann S, Hartmann A, Agaimy A, Haller F. Solitary fibrous tumors/hemangiopericytomas with different variants of the NAB2-STAT6 gene fusion are characterized by specific histomorphology and distinct clinicopathological features. Am J Pathol. 2014;184:1209–1218. doi: 10.1016/j.ajpath.2013.12.016.
    1. Schirosi L, Lantuejoul S, Cavazza A, Murer B, Yves Brichon P, Migaldi M, Sartori G, Sgambato A, Rossi G. Pleuro-pulmonary solitary fibrous tumors: a clinicopathologic, immunohistochemical, and molecular study of 88 cases confirming the prognostic value of de Perrot staging system and p53 expression, and evaluating the role of c-kit, BRAF, PDGFRs (alpha/beta), c-met, and EGFR. Am J Surg Pathol. 2008;32:1627–1642. doi: 10.1097/PAS.0b013e31817a8a89.
    1. England DM, Hochholzer L, McCarthy MJ. Localized benign and malignant fibrous tumors of the pleura. A clinicopathologic review of 223 cases. Am J Surg Pathol. 1989;13:640–658. doi: 10.1097/00000478-198908000-00003.
    1. Tapias LF, Mino-Kenudson M, Lee H, Wright C, Gaissert HA, Wain JC, Mathisen DJ, Lanuti M. Risk factor analysis for the recurrence of resected solitary fibrous tumours of the pleura: a 33-year experience and proposal for a scoring system. Eur J Cardiothorac Surg. 2013;44:111–117. doi: 10.1093/ejcts/ezs629.
    1. de Perrot M, Fischer S, Brundler MA, Sekine Y, Keshavjee S. Solitary fibrous tumors of the pleura. Ann Thorac Surg. 2002;74:285–293. doi: 10.1016/S0003-4975(01)03374-4.
    1. Vallat-Decouvelaere AV, Dry SM, Fletcher CD. Atypical and malignant solitary fibrous tumors in extrathoracic locations: evidence of their comparability to intra-thoracic tumors. Am J Surg Pathol. 1998;22:1501–1511. doi: 10.1097/00000478-199812000-00007.
    1. Franzen D, Diebold M, Soltermann A, Schneiter D, Kestenholz P, Stahel R, Weder W, Kohler M. Determinants of outcome of solitary fibrous tumors of the pleura: an observational cohort study. BMC Pulm Med. 2014;14:138. doi: 10.1186/1471-2466-14-138.
    1. van Houdt WJ, Westerveld CM, Vrijenhoek JE, van Gorp J, van Coevorden F, Verhoef C, van Dalen T. Prognosis of solitary fibrous tumors: a multicenter study. Ann Surg Oncol. 2013;20:4090–4095. doi: 10.1245/s10434-013-3242-9.
    1. Hiraoka K, Morikawa T, Ohbuchi T, Katoh H. Solitary fibrous tumors of the pleura: clinicopathological and immunohistochemical examination. Interact Cardiovasc Thorac Surg. 2003;2:61–64. doi: 10.1016/S1569-9293(02)00091-9.
    1. Yokoi T, Tsuzuki T, Yatabe Y, Suzuki M, Kurumaya H, Koshikawa T, Kuhara H, Kuroda M, Nakamura N, Nakatani Y, Kakudo K. Solitary fibrous tumour: significance of p53 and CD34 immunoreactivity in its malignant transformation. Histopathology. 1998;32:423–432. doi: 10.1046/j.1365-2559.1998.00412.x.
    1. Demicco EG, Harms PW, Patel RM, Smith SC, Ingram D, Torres K, Carskadon SL, Camelo-Piragua S, McHugh JB, Siddiqui J, et al. Extensive survey of STAT6 expression in a large series of mesenchymal tumors. Am J Clin Pathol. 2015;143:672–682. doi: 10.1309/AJCPN25NJTOUNPNF.
    1. Luporsi E, André F, Spyratos F, Martin PM, Jacquemier J, Penault-Llorca F, Tubiana-Mathieu N, Sigal-Zafrani B, Arnould L, Gompel A, et al. Ki-67: level of evidence and methodological considerations for its role in the clinical management of breast cancer: analytical and critical review. Breast Cancer Res Treat. 2012;132:895–915. doi: 10.1007/s10549-011-1837-z.
    1. Tollefson MK, Karnes RJ, Kwon ED, Lohse CM, Rangel LJ, Mynderse LA, Cheville JC, Sebo TJ. Prostate cancer Ki-67 (MIB-1) expression, perineural invasion, and gleason score as biopsy-based predictors of prostate cancer mortality: the Mayo model. Mayo Clin Proc. 2014;89:308–318. doi: 10.1016/j.mayocp.2013.12.001.

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