Assessment of diagnostic and prognostic factors in pancreatic duct carcinoma

Abstract: Assessment of Diagnostic and Prognostic Factors in Pancreatic Duct Carcinoma Stefan Linder, Department of Surgery, Stockholm Söder Hospital, Karolinska Institute, S-118 83 Stockholm, Sweden The diagnosis pancreatic carcinoma is suggested by a combination of clinical and radiological signs. The differential diagnosis vs. chronic pancreatitis may, however, be difficult. Morphological verification of malignancy is therefore necessary before initiating non-surgical therapy. The present study is focused on the use of cytological material in the diagnosis of pancreatic carcinoma and some tumour biological properties that may have a prognostic impact in patients with pancreatic carcinoma. A series of 334 patients with suspected pancreatic carcinoma underwent percutaneous fine-needle aspiration biopsy (FNAB). A malignant diagnosis was clenched in 270 and cytology was positive in 187. There were no false positive interpretations in 64 patients without a carcinoma. Thus, the sensitivity, specificity and overall accuracy were 69%, 100% and 75%, respectively. There were no complications or cutaneous metastases. FNAB can therefore be considered a safe and reliable procedure for confirming pretreatment diagnoses of pancreatic carcinoma. Morphometry was studied as an aid to conventional morphology in cytological material from 100 patients with pancreatic carcinoma and 15 with chronic pancreatitis. There were pronounced differences between the two patient groups and interobserver reproducibility was demonstrated. The results therefore indicate that morphometry may be used as an adjunct to conventional cytology in the diagnosis of pancreatic carcinoma. DNA ploidy was assessed by performing image cytometry (ICM) on cytological samples from 128 patients with pancreatic carcinoma. There were 39 (30%) DNA diploid, 21 (17%) tetraploid and 68 (53%) aneuploid tumours. Among patients who had undergone resection, the DNA pattern was diploid to a greater extent than among those who received non-surgical treatment. Prognostic information was obtained by DNA ploidy and morphometric variables alone, and in combination. The proliferating antigen Ki-67 and p53 protein expression were analysed by immunohistochemistry (IHC) performed on formalin-fixed paraffin-embedded tumour material. The p53 protein was expressed in 22 tumours (46%) while 26 (54%) were negative. Immunoreactivity of the Ki-67 antigen was evaluated by scoring and interactive image analyses (the proliferating cell index, PCI, and proliferating cell area, PCA, were calculated). All three variables correlated with survival time but only PCA and p53 protein expression had independent prognostic value. The expression of extracellular matrix (ECM) proteins and adhesion molecules was studied by IHC performed on frozen sections from 10 pancreatic carcinomas. Normal pancreas tissue served as control material. In contrast to the normal pancreas, the basement membrane in carcinomas was discontinuous as demonstrated by type IV collagen and laminin. These two ECM proteins, together with tenascin and vitronectin, were present in cancer cell areas of the stroma. Corresponding integrin receptors (a2, a3, a~) were expressed on cancer cells, thus providing possibilities for interactions and increased capacity for local invasiveness. Key words: Pancreatic neoplasms, cytology, diagnosis, prognosis, DNA ploidy, morphometry, immunohistochemistry, Ki-67 antigen, p53 protein, ECM proteins, adhesion molecules. ISBN 91-628-2352-3