Expression of inflammatory modulator COX-2 in pancreatic ductal adenocarcinoma and its relationship to pathologic and clinical parameters

Kambiz Merati, Mir Said Siadaty, Aleodor Andea, Fazlul Sarkar, Edgar Ben-Josef, Ramzi Mohammad, Philip Philip, Anthony F. Shields, Vainitus Vaitkevicius, David Grignon, N. Volkan Adsay

Research output: Contribution to journalArticle

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Abstract

Despite the exceedingly poor prognosis of pancreatic cancer, it is often histologically well to moderately differentiated. The apparent resistance to conventional therapeutic modalities is poorly understood and may be related to the molecules involved in its progression or its propensity for perineurial invasion. Cyclooxygenase-2 (COX-2) is an inducible enzyme homologous to COX-1 that is responsible for production of prostaglandins at sites of inflammation. It is activated by a variety of growth factors and tumor promoters, and it has been implicated in cancer progression. It may also have a role in the resistance to therapy. Anti-COX-2 agents have been documented to have antitumor activity, and some are now being tested in the therapy for various cancers, including those of the pancreas. Experience regarding the rate of COX-2 expression in pancreatic cancer and its relationship to the clinical and biologic parameters is very limited. In this study, immunohistochemical stains for COX-2 have been performed on 120 cases of pancreatic ductal adenocarcinoma. The stains were scored according to the percentage (0: no staining, 1: <10%, 2: 10-50%, and 3: >50% of the cells staining) and intensity (0 for no staining, 1 for mild staining, and 2 for dark staining) of staining. Based on the combined score for each case, they were divided into low expressors (percentage and intensity ≤1) and high expressors (percentage or intensity >1). In addition to global scoring for each case, the glandular and solid (poorly differentiated) components, when present, were scored separately. The global scores were correlated with clinical and biologic parameters. Seventy-four percent of the cases exhibited expression of COX-2 and 53% were high expressors. No significant association was observed when comparing the global COX-2 expression to survival, tumor size, stage, and vascular invasion. Increased perineural invasion was found to be significantly associated with COX-2 expression (p <0.05). Increased expression was also more common in the glandular component as compared with the solid component of the tumors (68% versus 35%, p <0.05). Of the 34 patients who received radiotherapy, 9 were low expressor (median survival 19.5 months) and 25 were high expressors (median survival 14 months). The difference in survival was not statistically significant.

Original languageEnglish (US)
Pages (from-to)447-452
Number of pages6
JournalAmerican Journal of Clinical Oncology: Cancer Clinical Trials
Volume24
Issue number5
DOIs
StatePublished - 2001
Externally publishedYes

Fingerprint

Cyclooxygenase 2
Adenocarcinoma
Staining and Labeling
Survival
Pancreatic Neoplasms
Neoplasms
Coloring Agents
Carcinogens
Prostaglandins
Blood Vessels
Pancreas
Intercellular Signaling Peptides and Proteins
Radiotherapy
Therapeutics
Inflammation
Enzymes

Keywords

  • Cyclooxygenase
  • Differentiation
  • Her2/neu
  • Immunohistochemistry
  • Pancreatic cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Expression of inflammatory modulator COX-2 in pancreatic ductal adenocarcinoma and its relationship to pathologic and clinical parameters. / Merati, Kambiz; Siadaty, Mir Said; Andea, Aleodor; Sarkar, Fazlul; Ben-Josef, Edgar; Mohammad, Ramzi; Philip, Philip; Shields, Anthony F.; Vaitkevicius, Vainitus; Grignon, David; Adsay, N. Volkan.

In: American Journal of Clinical Oncology: Cancer Clinical Trials, Vol. 24, No. 5, 2001, p. 447-452.

Research output: Contribution to journalArticle

Merati, Kambiz ; Siadaty, Mir Said ; Andea, Aleodor ; Sarkar, Fazlul ; Ben-Josef, Edgar ; Mohammad, Ramzi ; Philip, Philip ; Shields, Anthony F. ; Vaitkevicius, Vainitus ; Grignon, David ; Adsay, N. Volkan. / Expression of inflammatory modulator COX-2 in pancreatic ductal adenocarcinoma and its relationship to pathologic and clinical parameters. In: American Journal of Clinical Oncology: Cancer Clinical Trials. 2001 ; Vol. 24, No. 5. pp. 447-452.
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AU - Mohammad, Ramzi

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AU - Adsay, N. Volkan

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N2 - Despite the exceedingly poor prognosis of pancreatic cancer, it is often histologically well to moderately differentiated. The apparent resistance to conventional therapeutic modalities is poorly understood and may be related to the molecules involved in its progression or its propensity for perineurial invasion. Cyclooxygenase-2 (COX-2) is an inducible enzyme homologous to COX-1 that is responsible for production of prostaglandins at sites of inflammation. It is activated by a variety of growth factors and tumor promoters, and it has been implicated in cancer progression. It may also have a role in the resistance to therapy. Anti-COX-2 agents have been documented to have antitumor activity, and some are now being tested in the therapy for various cancers, including those of the pancreas. Experience regarding the rate of COX-2 expression in pancreatic cancer and its relationship to the clinical and biologic parameters is very limited. In this study, immunohistochemical stains for COX-2 have been performed on 120 cases of pancreatic ductal adenocarcinoma. The stains were scored according to the percentage (0: no staining, 1: <10%, 2: 10-50%, and 3: >50% of the cells staining) and intensity (0 for no staining, 1 for mild staining, and 2 for dark staining) of staining. Based on the combined score for each case, they were divided into low expressors (percentage and intensity ≤1) and high expressors (percentage or intensity >1). In addition to global scoring for each case, the glandular and solid (poorly differentiated) components, when present, were scored separately. The global scores were correlated with clinical and biologic parameters. Seventy-four percent of the cases exhibited expression of COX-2 and 53% were high expressors. No significant association was observed when comparing the global COX-2 expression to survival, tumor size, stage, and vascular invasion. Increased perineural invasion was found to be significantly associated with COX-2 expression (p <0.05). Increased expression was also more common in the glandular component as compared with the solid component of the tumors (68% versus 35%, p <0.05). Of the 34 patients who received radiotherapy, 9 were low expressor (median survival 19.5 months) and 25 were high expressors (median survival 14 months). The difference in survival was not statistically significant.

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