Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Clinical Sarcoma Research
Published in: Clinical Sarcoma Research 1/2017

Open Access 01-12-2017 | Research

Utility of VS38c in the diagnostic and prognostic assessment of osteosarcoma and other bone tumours/tumour-like lesions

Authors: E. S. Hookway, Z. Orosz, Y. Uchihara, A. Grigoriadis, A. B. Hassan, U. Oppermann, N. A. Athanasou

Published in: Clinical Sarcoma Research | Issue 1/2017

Login to get access

Abstract

Background

VS38c is a monoclonal antibody that recognises a rough endoplasmic reticulum (rER) intracellular antigen termed cytoskeleton-linking membrane protein 63. rER is typically found in viable tumour cells and is abundant in osteosarcoma cells. The aim of this study was to determine the diagnostic and prognostic utility of VS38c in the histological assessment of osteosarcoma and other bone tumours/tumour-like leisons.

Methods

Immunohistochemical staining with VS38c was carried out on formalin-fixed specimens of osteosarcoma (pre/post-chemotherapy) and a wide range of benign and malignant bone lesions. In addition, VS38c staining of cultures of MG63 and Sa0S2 osteosarcoma cell cultures. (±cisplatin and actinomycin D-treatment) was analysed.

Results

VS38c strongly stained tumour cells in all low-grade and high-grade osteosarcomas and in undifferentiated sarcomas and high-grade chondrosarcomas. There was little or no VS38c staining of low-grade chondrosarcomas or chordomas and variable staining of Ewing sarcomas. Osteoblasts in benign bone-forming tumours and mononuclear stromal cells in chondroblastomas, giant cell tumours and non-ossifying fibromas strongly stained for VS38c. VS38c staining was absent in cisplatin and actinomycin D treated Sa0S2 and MG63 cells. In specimens of osteosarcoma post-neoadjuvant therapy, VS38c staining was absent in most morphologically necrotic areas of tumor although some cells with pyknotic nuclei stained for VS38c in these areas. Most tumour cells exhibiting atypical nuclear forms were not stained by VS38c.

Conclusions

Our findings show that VS38c is a sensitive but not specific diagnostic marker of osteosarcoma. Staining with VS38c identifies viable osteosarcoma cells, a feature which may be useful in the assessment of percentage tumour necrosis post-neoadjuvant chemotherapy.
Literature
1.
2.
Turley H, Jones M, Erber W, Mayne K, de Waele M, Gatter K. VS38: a new monoclonal antibody for detecting plasma cell differentiation in routine sections. J Clin Pathol. 1994;47:418–22.CrossRefPubMedPubMedCentral
3.
Banham AH, Turley H, Pulford K, Gatter K, Mason DY. The plasma cell associated antigen detectable by antibody VS38 is the p63 rough endoplasmic reticulum protein. J Clin Pathol. 1997;50:485–9.CrossRefPubMedPubMedCentral
4.
Banerjee SS, Shanks JH, Hasleton PS. VS38 immunostaining in neuroendocrine tumours. Histopathology. 1997;30:256–9.CrossRefPubMed
5.
Sulzbacher I, Fuchs M, Chott A, Lang S. Expression of VS38 in osteoblasts and stroma cells of bone tumors. Pathol Res Pract. 1997;193:613–6.CrossRefPubMed
6.
7.
8.
Orvoine RH, Messier PE, Cantin M, Seidman JM. Light and electron microscope study of osmotically induced tumor necrosis. Cancer Res. 1978;38:1960–6.PubMed
9.
Pelletier N, Casamayor-Pallejà M, De Luca K, Mondière P, Saltel F, Jurdic P, et al. The endoplasmic reticulum is a key component of the plasma cell death pathway. J Immunol. 2006;176:1340–7.CrossRefPubMed
10.
Galluzzi L, Maiuri MC, Vitale I, Zischka H, Castedo M, Zitvogel L, et al. Cell death modalities: classification and pathophysiological implications. Cell Death Differ. 2007;14:1237–43.CrossRefPubMed
11.
Kroemer G, Galluzzi L, Vandenabeele P, Abrams J, Alnemri ES, Baehrecke EH, et al. Classification of cell death: recommendations of the Nomenclature Committee on cell death. Cell Death Differ. 2009;16:3–11.CrossRefPubMed
12.
Chiu H-W, Tseng Y-C, Hsu Y-H, Lin Y-F, Foo N-P, Guo H-R, et al. Arsenic trioxide induces programmed cell death through stimulation of ER stress and inhibition of the ubiquitin–proteasome system in human sarcoma cells. Cancer Lett. 2015;356:762–72.CrossRefPubMed
13.
Kamiński M, Masaoka M, Karbowski M, Kedzior J, Nishizawa Y, Usukura J, et al. Ultrastructural basis for the transition of cell death mode from apoptosis to necrosis in menadione-treated osteosarcoma 143B cells. J Electron Microsc (Tokyo). 2003;52:313–25.CrossRef
14.
Tao H, Tao L, Shen C, Liu B, Yang Z, Tao H. Silencing of Barkor/ATG14 sensitizes osteosarcoma cells to cisplatin-induced apoptosis. Int J Mol Med. 2013;33:271–6.PubMedPubMedCentral
15.
Rosen G, Caparros B, Huvos AG, Kosloff C, Nirenberg A, Cacavio A, et al. Preoperative chemotherapy for osteogenic sarcoma: selection of postoperative adjuvant chemotherapy based on the response of the primary tumor to preoperative chemotherapy. Cancer. 1982;49:1221–30.CrossRefPubMed
16.
Raymond AK, Chawla SP, Carrasco CH, Ayala AG, Fanning CV, Grice B, et al. Osteosarcoma chemotherapy effect: a prognostic factor. Semin Diagn Pathol. 1987;4:212–36.PubMed
17.
Bramwell VH, Burgers M, Sneath R, Souhami R, van Oosterom AT, Voûte PA, et al. A comparison of two short intensive adjuvant chemotherapy regimens in operable osteosarcoma of limbs in children and young adults: the first study of the European Osteosarcoma Intergroup. J Clin Oncol. 1992;10:1579–91.CrossRefPubMed
18.
Davis AM, Bell RS, Goodwin PJ. Prognostic factors in osteosarcoma: a critical review. J Clin Oncol. 1994;12:423–31.CrossRefPubMed
19.
Saeter G, Elomaa I, Wahlqvist Y, Alvegård TA, Wiebe T, Monge O, et al. Prognostic factors in bone sarcomas. Acta Orthop Scand. 1997;68(Suppl 273):156–60.CrossRef
20.
Patterson K. The pathologic handling of skeletal tumors. Am J Clin Pathol. 1998;109(4 Suppl 1):S53–66.PubMed
21.
Wold LE. Practical approach to processing osteosarcomas in the surgical pathology laboratory. Pediatr Dev Pathol. 1998;1:449–54.CrossRefPubMed
22.
Huvos AG, Rosen G, Marcove RC. Primary osteogenic sarcoma: pathologic aspects in 20 patients after treatment with chemotherapy en bloc resection, and prosthetic bone replacement. Arch Pathol Lab Med. 1977;101:14–8.PubMed
23.
Picci P, Bacci G, Campanacci M, Gasparini M, Pilotti S, Cerasoli S, et al. Histologic evaluation of necrosis in osteosarcoma induced by chemotherapy. Regional mapping of viable and nonviable tumor. Cancer. 1985;56:1515–21.CrossRefPubMed
24.
Ayala AG, Raymond AK, Jaffe N. The pathologist’s role in the diagnosis and treatment of osteosarcoma in children. Hum Pathol. 1984;15:258–66.CrossRefPubMed
25.
Weatherby RP, Unni KK. Practical aspects of handling orthopedic specimens in the surgical pathology laboratory. Pathol Annu. 1982;17(Pt 2):1–31.PubMed
26.
Coffin CM, Lowichik A, Zhou H. Treatment effects in pediatric soft tissue and bone tumors. Am J Clin Pathol. 2005;123:75–90.CrossRefPubMed
27.
Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F. editors. WHO classification of tumours of soft tissue and bone, 4th edn. Lyon: IARC; 2013.
28.
Athanasou NA. Cell and organ culture in the understanding of the bone and its neoplasms. In: Helliwell TR, editors. Pathology of bone and joint neoplasms. Saunders: Philadelphia; 1999. p. 34–58.
29.
Dahlin DC. Osteosarcoma of bone and a consideration of prognostic variables. Cancer Treat Rep. 1978;62:189–92.PubMed
30.
Goidanich IF, Battaglia L, Lenzi L, Silva E. Osteogenic sarcoma analysis of factors influencing prognosis in 100 cases. Clin Orthop Relat Res. 1966;48:209–22.PubMed
31.
Hauben EI, Weeden S, Pringle J, Van Marck EA, Hogendoorn PCW. Does the histological subtype of high-grade central osteosarcoma influence the response to treatment with chemotherapy and does it affect overall survival? A study on 570 patients of two consecutive trials of the European Osteosarcoma Intergroup. Eur J Cancer. 2002;38:1218–25.CrossRefPubMed
32.
Bacci G, Bertoni F, Longhi A, Ferrari S, Forni C, Biagini R, et al. Neoadjuvant chemotherapy for high-grade central osteosarcoma of the extremity. Cancer. 2003;97:3068–75.CrossRefPubMed
33.
Glasser DB, Lane JM, Huvos AG, Marcove RC, Rosen G. Survival, prognosis, and therapeutic response in osteogenic sarcoma. The Memorial Hospital experience. Cancer. 1992;69:698–708.CrossRefPubMed
34.
Rosen G, Marcove RC, Caparros B, Nirenberg A, Kosloff C, Huvos AG. Primary osteogenic sarcoma: the rationale for preoperative chemotherapy and delayed surgery. Cancer. 1979;43:2163–77.CrossRefPubMed
35.
Benjamin RS, Chawla SP, Carrasco CH, Raymond AK, Murray JA, Armen T, et al. Preoperative chemotherapy for osteosarcoma with intravenous adriamycin and intra-arterial cis-platinum. Ann Oncol. 1992;3(suppl_2):S3–6.CrossRefPubMed
36.
Willén H. Tumor necrosis and prognosis in osteosarcoma. Acta Orthop Scand. 1997;68(Suppl 273):126–9.CrossRef
Metadata
Title
Utility of VS38c in the diagnostic and prognostic assessment of osteosarcoma and other bone tumours/tumour-like lesions
Authors
E. S. Hookway
Z. Orosz
Y. Uchihara
A. Grigoriadis
A. B. Hassan
U. Oppermann
N. A. Athanasou
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Clinical Sarcoma Research / Issue 1/2017
Electronic ISSN: 2045-3329
DOI
https://doi.org/10.1186/s13569-017-0083-5

Other articles of this Issue 1/2017

Clinical Sarcoma Research 1/2017 Go to the issue

Research

IDH1 or -2 mutations do not predict outcome and do not cause loss of 5-hydroxymethylcytosine or altered histone modifications in central chondrosarcomas

Review

UK clinical practice guidelines for the management of gastrointestinal stromal tumours (GIST)

Research

A retrospective cohort study of treatment patterns among patients with metastatic soft tissue sarcoma in the US

Case report

Complete response of mediastinal clear cell sarcoma to pembrolizumab with radiotherapy

Case report

Two years survival of primary cardiac leiomyosarcoma managed by surgical and adjuvant therapy

Research

Antiangiogenic effects in patients with progressive desmoplastic small round cell tumor: data from the French national registry dedicated to the use of off-labeled targeted therapy in sarcoma (OUTC’s)
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits