Heat Shock Protein 90 (HSP90) Expression in Pancreatic Endocrine Neoplasms: A Potential Therapeutic Target and Predictor of Behavior.
Abel A Gonzalez-Longoria, Hellen Remotti. Columbia University Medical Center, New York, NY
Background: HSPs are molecular chaperones which facilitate tumor growth and resistance to radiation/chemotherapy. Hsp90 antagonists are being pursued in therapeutic trials. Scant data is available regarding HSP expression in Pancreatic Endocrine Neoplasms (PEN). We evaluated the expression of Hsp90 in PEN by immunohistochemistry.
Design: Representative tissue microarrays from paraffin blocks of 58 PEN representing 26 PEN localized low grade (PENL), 13 PEN localized with vascular invasion (PENVI) and 19 malignant cases with metastasis to liver or lymph nodes (PENM) were immunostained with antibodies to Hsp 90. Expression of Hsp90 was validated on endometrium and internal pancreatic ductal and islet controls. The intensity of cytoplasmic and nuclear Hsp90 expression of tumor cells was compared with non-neoplastic pancreatic islet cells and semiquantitatively scored, as 0= less than or negative, 1= similar to, and 2= greater than non-neoplastic islet cells.
Results: The immunoreactivity was cytoplasmic and nuclear. The percentage of positive cases is tabulated. Among every case studied, cytoplasmic Hsp90 was diffusely expressed with a score of 1 and 2 in 100% of cases with PENL and PENVI and 95% (18 /19) cases of PENM. Nuclear Hsp90 showed more variation. The overall mean percent of tumor with positive nuclear staining was higher (score 1-2) in angioinvasive (PENVI) and metastatic (PENM) as compared to low-grade PEN: PENL 69%, PENVI 92% and PENM 89% (p=0.04) (see Table).
|Tumor Type||Score 0 =less than normal islet or negative||Score 1 =similar to normal islet||Score 2=more than normal islet|
|PENL (26)||8 (31)||11 (42)||7 (27)|
|PENVI(13)||1 (8)||7 (54)||5 (38)|
|PENM (19)||2 (10)||7 (37)||10 (53)|
|Total = 58||11||25||22|