CD44 Loss in Gastric Stromal Tumors as a Prognostic Marker

Elizabeth Montgomery, Susan C. Abraham, Cyril Fisher, Mari Robinette Deasel, S. S. Amr, Salwa S. Sheikh, Michael House, Keith Lilliemoe, Michael Choti, Malcolm Brock, David T. Ephron, Mariana Zahuruk, Amy Chadburn

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Background: The adhesion molecule CD44 (CD44s; CD44H) and its isoforms (CD44v3-6 and v9) are preferentially expressed by different cell types. These transmembrane glycoproteins are involved in cell-cell and cell-matrix interactions and in cell trafficking and, thus, may play a role in tumor metastasis and/or local invasion. The expression pattern of CD44s and variant isoforms, particularly CD44v6 and CD44v9, of some neoplasms, including soft tissue tumors, correlates with clinical course and outcome. The clinical behavior of gastrointestinal stromal tumors (GIST) is site specific; however, other reliable predictors of clinical outcome have not been identified. Thus, the prognostic value of CD44s and isoform expression in GIST were evaluated by immunohistochemistry of tissue microarrays. Design: Paraffin-embedded formalin-fixed tissue cores (129: 103 GIST and 26 normal stomach smooth muscle) from 33 patients with clinical outcome data were collected and used for the construction of the tissue microarrays. One to five tissue cores from each patient specimen were evaluated (mean = 3 tissue cores/patient). Array slides were stained with anti-CD44s (CD44H) and with antibodies to v3, v4, v5, v6, and v9 isomers. CD44s and isoform expression and staining intensity were scored semiquantitatively without knowledge of patient identity or outcome: 0 = no; 1 = weak; 2 = moderate; 3 = moderate to strong; 4 = strong. The scores of multiple cores from the same GIST were averaged; the nonneoplastic smooth muscle was similarly graded. CD44s and isoform expression and intensity were compared with outcome. Results: The 33 patients with gastric GIST, 0.8 to 30 cm in size, were followed for 1 to 111 months with a median follow-up of 7 months (mean 17.5 months). The overall median survival was 25 months. Nine of the 33 (27%) patients had metastases, 9 (27%) had recurrent disease, and 9 (27%) died of disease (9-111 months; mean 39 months; median 23 months). All 18 patients with GIST CD44s expression >2+ were alive at last follow-up (1-62 months; median 3.5 months; mean 11 months). More than half (53%) of patients with GIST CD44s expression ≤2+ died (9-111 months; median 23 months; mean 38 months); the median follow-up of the surviving patients with CD44 expression ≤2 was 5 months (2-22 months; mean 6.5 months; log rank P = 0.07). The majority of tumors were variably positive CD44v3 and CD44v4, but there was minimal staining (number of cases and/or expression level) with antibodies directed against the v5, v6, and v9 isomers. Conclusion: These preliminary results suggest that although gastric GISTs variably express CD44s and variants, only the expression of CD44s correlates with clinical outcome with loss of CD44s positivity correlating with poor clinical outcome.

Original languageEnglish (US)
Pages (from-to)168-177
Number of pages10
JournalAmerican Journal of Surgical Pathology
Volume28
Issue number2
DOIs
StatePublished - Feb 2004
Externally publishedYes

Fingerprint

Gastrointestinal Stromal Tumors
Stomach
Protein Isoforms
Neoplasms
Smooth Muscle
Soft Tissue Neoplasms
Staining and Labeling
Neoplasm Metastasis
Antibodies
Cell Communication
Paraffin
Formaldehyde
Glycoproteins
Immunohistochemistry
Survival

Keywords

  • CD44
  • Gastrointestinal stromal tumors
  • Prognostic markers

ASJC Scopus subject areas

  • Anatomy
  • Pathology and Forensic Medicine

Cite this

Montgomery, E., Abraham, S. C., Fisher, C., Deasel, M. R., Amr, S. S., Sheikh, S. S., ... Chadburn, A. (2004). CD44 Loss in Gastric Stromal Tumors as a Prognostic Marker. American Journal of Surgical Pathology, 28(2), 168-177. https://doi.org/10.1097/00000478-200402000-00003

CD44 Loss in Gastric Stromal Tumors as a Prognostic Marker. / Montgomery, Elizabeth; Abraham, Susan C.; Fisher, Cyril; Deasel, Mari Robinette; Amr, S. S.; Sheikh, Salwa S.; House, Michael; Lilliemoe, Keith; Choti, Michael; Brock, Malcolm; Ephron, David T.; Zahuruk, Mariana; Chadburn, Amy.

In: American Journal of Surgical Pathology, Vol. 28, No. 2, 02.2004, p. 168-177.

Research output: Contribution to journalArticle

Montgomery, E, Abraham, SC, Fisher, C, Deasel, MR, Amr, SS, Sheikh, SS, House, M, Lilliemoe, K, Choti, M, Brock, M, Ephron, DT, Zahuruk, M & Chadburn, A 2004, 'CD44 Loss in Gastric Stromal Tumors as a Prognostic Marker', American Journal of Surgical Pathology, vol. 28, no. 2, pp. 168-177. https://doi.org/10.1097/00000478-200402000-00003
Montgomery E, Abraham SC, Fisher C, Deasel MR, Amr SS, Sheikh SS et al. CD44 Loss in Gastric Stromal Tumors as a Prognostic Marker. American Journal of Surgical Pathology. 2004 Feb;28(2):168-177. https://doi.org/10.1097/00000478-200402000-00003
Montgomery, Elizabeth ; Abraham, Susan C. ; Fisher, Cyril ; Deasel, Mari Robinette ; Amr, S. S. ; Sheikh, Salwa S. ; House, Michael ; Lilliemoe, Keith ; Choti, Michael ; Brock, Malcolm ; Ephron, David T. ; Zahuruk, Mariana ; Chadburn, Amy. / CD44 Loss in Gastric Stromal Tumors as a Prognostic Marker. In: American Journal of Surgical Pathology. 2004 ; Vol. 28, No. 2. pp. 168-177.
@article{802d652d216c4cf1bf4c1e482cc55477,
title = "CD44 Loss in Gastric Stromal Tumors as a Prognostic Marker",
abstract = "Background: The adhesion molecule CD44 (CD44s; CD44H) and its isoforms (CD44v3-6 and v9) are preferentially expressed by different cell types. These transmembrane glycoproteins are involved in cell-cell and cell-matrix interactions and in cell trafficking and, thus, may play a role in tumor metastasis and/or local invasion. The expression pattern of CD44s and variant isoforms, particularly CD44v6 and CD44v9, of some neoplasms, including soft tissue tumors, correlates with clinical course and outcome. The clinical behavior of gastrointestinal stromal tumors (GIST) is site specific; however, other reliable predictors of clinical outcome have not been identified. Thus, the prognostic value of CD44s and isoform expression in GIST were evaluated by immunohistochemistry of tissue microarrays. Design: Paraffin-embedded formalin-fixed tissue cores (129: 103 GIST and 26 normal stomach smooth muscle) from 33 patients with clinical outcome data were collected and used for the construction of the tissue microarrays. One to five tissue cores from each patient specimen were evaluated (mean = 3 tissue cores/patient). Array slides were stained with anti-CD44s (CD44H) and with antibodies to v3, v4, v5, v6, and v9 isomers. CD44s and isoform expression and staining intensity were scored semiquantitatively without knowledge of patient identity or outcome: 0 = no; 1 = weak; 2 = moderate; 3 = moderate to strong; 4 = strong. The scores of multiple cores from the same GIST were averaged; the nonneoplastic smooth muscle was similarly graded. CD44s and isoform expression and intensity were compared with outcome. Results: The 33 patients with gastric GIST, 0.8 to 30 cm in size, were followed for 1 to 111 months with a median follow-up of 7 months (mean 17.5 months). The overall median survival was 25 months. Nine of the 33 (27{\%}) patients had metastases, 9 (27{\%}) had recurrent disease, and 9 (27{\%}) died of disease (9-111 months; mean 39 months; median 23 months). All 18 patients with GIST CD44s expression >2+ were alive at last follow-up (1-62 months; median 3.5 months; mean 11 months). More than half (53{\%}) of patients with GIST CD44s expression ≤2+ died (9-111 months; median 23 months; mean 38 months); the median follow-up of the surviving patients with CD44 expression ≤2 was 5 months (2-22 months; mean 6.5 months; log rank P = 0.07). The majority of tumors were variably positive CD44v3 and CD44v4, but there was minimal staining (number of cases and/or expression level) with antibodies directed against the v5, v6, and v9 isomers. Conclusion: These preliminary results suggest that although gastric GISTs variably express CD44s and variants, only the expression of CD44s correlates with clinical outcome with loss of CD44s positivity correlating with poor clinical outcome.",
keywords = "CD44, Gastrointestinal stromal tumors, Prognostic markers",
author = "Elizabeth Montgomery and Abraham, {Susan C.} and Cyril Fisher and Deasel, {Mari Robinette} and Amr, {S. S.} and Sheikh, {Salwa S.} and Michael House and Keith Lilliemoe and Michael Choti and Malcolm Brock and Ephron, {David T.} and Mariana Zahuruk and Amy Chadburn",
year = "2004",
month = "2",
doi = "10.1097/00000478-200402000-00003",
language = "English (US)",
volume = "28",
pages = "168--177",
journal = "American Journal of Surgical Pathology",
issn = "0147-5185",
publisher = "Lippincott Williams and Wilkins",
number = "2",

}

TY - JOUR

T1 - CD44 Loss in Gastric Stromal Tumors as a Prognostic Marker

AU - Montgomery, Elizabeth

AU - Abraham, Susan C.

AU - Fisher, Cyril

AU - Deasel, Mari Robinette

AU - Amr, S. S.

AU - Sheikh, Salwa S.

AU - House, Michael

AU - Lilliemoe, Keith

AU - Choti, Michael

AU - Brock, Malcolm

AU - Ephron, David T.

AU - Zahuruk, Mariana

AU - Chadburn, Amy

PY - 2004/2

Y1 - 2004/2

N2 - Background: The adhesion molecule CD44 (CD44s; CD44H) and its isoforms (CD44v3-6 and v9) are preferentially expressed by different cell types. These transmembrane glycoproteins are involved in cell-cell and cell-matrix interactions and in cell trafficking and, thus, may play a role in tumor metastasis and/or local invasion. The expression pattern of CD44s and variant isoforms, particularly CD44v6 and CD44v9, of some neoplasms, including soft tissue tumors, correlates with clinical course and outcome. The clinical behavior of gastrointestinal stromal tumors (GIST) is site specific; however, other reliable predictors of clinical outcome have not been identified. Thus, the prognostic value of CD44s and isoform expression in GIST were evaluated by immunohistochemistry of tissue microarrays. Design: Paraffin-embedded formalin-fixed tissue cores (129: 103 GIST and 26 normal stomach smooth muscle) from 33 patients with clinical outcome data were collected and used for the construction of the tissue microarrays. One to five tissue cores from each patient specimen were evaluated (mean = 3 tissue cores/patient). Array slides were stained with anti-CD44s (CD44H) and with antibodies to v3, v4, v5, v6, and v9 isomers. CD44s and isoform expression and staining intensity were scored semiquantitatively without knowledge of patient identity or outcome: 0 = no; 1 = weak; 2 = moderate; 3 = moderate to strong; 4 = strong. The scores of multiple cores from the same GIST were averaged; the nonneoplastic smooth muscle was similarly graded. CD44s and isoform expression and intensity were compared with outcome. Results: The 33 patients with gastric GIST, 0.8 to 30 cm in size, were followed for 1 to 111 months with a median follow-up of 7 months (mean 17.5 months). The overall median survival was 25 months. Nine of the 33 (27%) patients had metastases, 9 (27%) had recurrent disease, and 9 (27%) died of disease (9-111 months; mean 39 months; median 23 months). All 18 patients with GIST CD44s expression >2+ were alive at last follow-up (1-62 months; median 3.5 months; mean 11 months). More than half (53%) of patients with GIST CD44s expression ≤2+ died (9-111 months; median 23 months; mean 38 months); the median follow-up of the surviving patients with CD44 expression ≤2 was 5 months (2-22 months; mean 6.5 months; log rank P = 0.07). The majority of tumors were variably positive CD44v3 and CD44v4, but there was minimal staining (number of cases and/or expression level) with antibodies directed against the v5, v6, and v9 isomers. Conclusion: These preliminary results suggest that although gastric GISTs variably express CD44s and variants, only the expression of CD44s correlates with clinical outcome with loss of CD44s positivity correlating with poor clinical outcome.

AB - Background: The adhesion molecule CD44 (CD44s; CD44H) and its isoforms (CD44v3-6 and v9) are preferentially expressed by different cell types. These transmembrane glycoproteins are involved in cell-cell and cell-matrix interactions and in cell trafficking and, thus, may play a role in tumor metastasis and/or local invasion. The expression pattern of CD44s and variant isoforms, particularly CD44v6 and CD44v9, of some neoplasms, including soft tissue tumors, correlates with clinical course and outcome. The clinical behavior of gastrointestinal stromal tumors (GIST) is site specific; however, other reliable predictors of clinical outcome have not been identified. Thus, the prognostic value of CD44s and isoform expression in GIST were evaluated by immunohistochemistry of tissue microarrays. Design: Paraffin-embedded formalin-fixed tissue cores (129: 103 GIST and 26 normal stomach smooth muscle) from 33 patients with clinical outcome data were collected and used for the construction of the tissue microarrays. One to five tissue cores from each patient specimen were evaluated (mean = 3 tissue cores/patient). Array slides were stained with anti-CD44s (CD44H) and with antibodies to v3, v4, v5, v6, and v9 isomers. CD44s and isoform expression and staining intensity were scored semiquantitatively without knowledge of patient identity or outcome: 0 = no; 1 = weak; 2 = moderate; 3 = moderate to strong; 4 = strong. The scores of multiple cores from the same GIST were averaged; the nonneoplastic smooth muscle was similarly graded. CD44s and isoform expression and intensity were compared with outcome. Results: The 33 patients with gastric GIST, 0.8 to 30 cm in size, were followed for 1 to 111 months with a median follow-up of 7 months (mean 17.5 months). The overall median survival was 25 months. Nine of the 33 (27%) patients had metastases, 9 (27%) had recurrent disease, and 9 (27%) died of disease (9-111 months; mean 39 months; median 23 months). All 18 patients with GIST CD44s expression >2+ were alive at last follow-up (1-62 months; median 3.5 months; mean 11 months). More than half (53%) of patients with GIST CD44s expression ≤2+ died (9-111 months; median 23 months; mean 38 months); the median follow-up of the surviving patients with CD44 expression ≤2 was 5 months (2-22 months; mean 6.5 months; log rank P = 0.07). The majority of tumors were variably positive CD44v3 and CD44v4, but there was minimal staining (number of cases and/or expression level) with antibodies directed against the v5, v6, and v9 isomers. Conclusion: These preliminary results suggest that although gastric GISTs variably express CD44s and variants, only the expression of CD44s correlates with clinical outcome with loss of CD44s positivity correlating with poor clinical outcome.

KW - CD44

KW - Gastrointestinal stromal tumors

KW - Prognostic markers

UR - http://www.scopus.com/inward/record.url?scp=9144238093&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=9144238093&partnerID=8YFLogxK

U2 - 10.1097/00000478-200402000-00003

DO - 10.1097/00000478-200402000-00003

M3 - Article

VL - 28

SP - 168

EP - 177

JO - American Journal of Surgical Pathology

JF - American Journal of Surgical Pathology

SN - 0147-5185

IS - 2

ER -