Detection of somatostatin receptors in surgical and percutaneous needle biopsy samples of carcinoids and islet cell carcinomas.

Somatostatin (SS) receptor status was investigated in the tumor tissues from 62 patients with carcinoid tumors and 15 patients with islet cell carcinomas using receptor autoradiography techniques with two different iodinated somatostatin analogues as radioligands, a [Leu8, DTrp22, Tyr25]somatostatin-28 and a somatostatin octapeptide, Tyr3-octreotide. The carcinoid tumors were either primaries (n = 32) or metastases (n = 43), sampled as surgical specimens or as small needle liver biopsies. Fifty-four of 62 carcinoid patients had SS receptor-positive tumors (87%). All 15 islet cell carcinoma patients had positive tumors (4 primaries, 11 metastases), i.e., 3 vipomas, 3 insulinomas, 2 glucagonomas, 1 gastrinoma, 2 polyfunctional tumors, and 4 nonfunctioning tumors. Saturation and competition experiments on tissue sections revealed saturable, high affinity binding sites pharmacologically specific for bioactive SS analogues. In a majority of the tumors, the receptors were densely distributed and were always homogeneously found in the whole tumor. All except two tumors were labeled with both radioligands. Multiple liver metastases (n = 16) from three different patients were all shown to contain a comparable amount of receptors. SS receptors could be demonstrated even in very small tissue samples of liver metastases obtained by percutaneous liver biopsies (mean weight, 6.8 mg). The majority of the eight SS receptor-negative carcinoids were mainly bronchial carcinoids (n = 5), usually poorly differentiated. On the contrary, SS receptor-positive cases were never found to be anaplastic. All tumors except one from patients pretreated with octreotide (3 days to 3.8 years) were SS receptor positive. In the majority of carcinoids or islet cell carcinomas, the SS receptor status correlated with the in vivo biochemical response (hormone inhibition) to octreotide. These data demonstrate (a) the high prevalence of SS receptors in the primary tumors of both carcinoids and islet cell carcinomas, (b) their presence in metastases as well, (c) their continuous expression even during long term octreotide therapy, (d) the possibility of measuring SS receptors in percutaneous needle liver biopsies, and (e) the evidence of their functionality. This study therefore suggests that tumoral SS receptors may be the likely molecular basis for octreotide action and may be an important parameter for predicting the therapeutic efficacy of SS analogues in carcinoids and islet cell carcinomas.

Characterization of the shed form of the human tumor-associated glycoprotein (TAG-72) from serous effusions of patients with different types of carcinomas.

Monoclonal antibody (MAb) B72.3 binds a high molecular weight tumor-associated glycoprotein designated TAG-72. This study reports the isolation and characterization of secreted TAG-72 directly from effusions of ovarian, colorectal, pancreatic, and endometrial carcinoma patients and compares them to TAG-72 derived from the LS-174T colon carcinoma xenograft. The B72.3-reactive antigen, TAG-72, was used as immunogen to produce second generation anti-TAG-72 MAbs. One of these second generation MAbs, CC49, had a higher affinity than that of B72.3 and was utilized as an affinity reagent in a procedure to purify the TAG-72 present in the serous effusions of carcinoma patients. A three-step purification procedure, utilizing heat extraction, CC49 antibody affinity chromatography, and gel filtration chromatography, resulted in 1000- to 4400-fold purifications of the TAG-72 derived from effusions, as analyzed using a double-determinant radioimmunoassay. Radiolabeled TAG-72 from each of the effusions demonstrated similar high molecular weight bands on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Similar results from the various effusions were also obtained in Western blotting analyses. Analyses of TAG-72 from the different effusions in radioimmunoassay using five different anti-TAG-72 MAbs revealed similar binding patterns. The results of these studies thus indicate that TAG-72 obtained directly from patients with ovarian, colorectal, endometrial, and pancreatic carcinomas and the LS-174T xenograft are highly similar in terms of immunochemical properties and antigenic profile.

Protein HMG-17 is hyper-expressed in rat glucagonoma. Single-step isolation and sequencing.

High-mobility-group protein 17 (HMG-17) was identified by reversed-phase high-performance liquid chromatography analysis as a major component in acidic extracts of transplantable rat glucagonoma tissue but not in insulinoma tissue of similar origin. The peptide was purified in a single step and the entire sequence of 89 amino acids was determined. Rat HMG-17 has a molecular mass of 9238 Da and shows strong similarity to human, bovine (94.4%) and chicken (88.8%) HMG-17. Six of the seven residues which vary among the mammalian sequences are located within a short segment (positions 64-83) present in the acidic, non-DNA-binding C-terminal part of HMG-17. This region shows least similarity to the otherwise related proteins HMG-14 and H6 (a trout HMG protein). Interestingly, four of the six variable positions are Asp in rat HMG-17 which results in an overall net increase in the negative charge of the C-terminal region. The nature of selective hyper-expression of HMG-17 in glucagon but not in insulin-producing tumor tissue remains to be clarified.

Identification in extracts from AR4-2J cells of inositol 1,4,5-trisphosphate by its susceptibility to inositol 1,4,5-trisphosphate 3-kinase and 5-phosphatase.

The identity of 3H-labelled material ascribed to Ins(1,4,5)P3 in resting or bombesin-stimulated myo-[3H]inositol-labelled AR4-2J cells was investigated by determining its ability to serve as substrate for partially purified Ins(1,4,5)P3/Ins(1,3,4,5)-P4 5-phosphatase and Ins(1,4,5)P3 3-kinase. This 3H-labelled material was metabolized by these two enzymes at rates which were indistinguishable from those for an internal [32P]Ins(1,4,5)P3 standard, establishing its identity as authentic Ins(1,4,5)P3. In addition, and in contrast with findings in earlier studies utilizing substance P as an agonist, prolonged stimulation with bombesin resulted in an increase in an InsP4 which was degraded by Ins(1,4,5)P3/Ins(1,3,4,5)P4 5-phosphatase. These findings serve to confirm the previous estimate of Horstman, Takemura & Putney [(1988) J. Biol. Chem. 263, 15297-15303] for the intracellular concentrations of Ins(1,4,5)P3 in resting (2 microM) and agonist-stimulated (25 microM) AR4-2J cells. The implications of these findings for the physiological regulation of intracellular Ca2+ through this intracellular messenger are discussed.

Nuclear DNA distribution pattern of the parenchymal cells in adenocarcinomas of the pancreas and in chronic pancreatitis. A study of archival specimens using both image and flow cytometry.

The nuclear DNA distribution pattern of the neoplastic parenchymal cells of 100 conventionally formalin-fixed and paraffin-embedded specimens from pancreatic adenocarcinomas and from 8 specimens of chronic pancreatitis was assessed by means of image cytometry. All material originated from pancreatic restrictions. Evaluable DNA histograms could be obtained for 77 carcinomas, and clinical data were available for 71 of these. In these 71 specimens, the nuclear DNA ploidy pattern was also investigated by means of flow cytometry. In 76 of the 77 cases, the image-cytometric DNA ploidy pattern obtained showed a "nondiploid" distribution with modal values as high as 8.5 c. In 21 cases, the neoplastic cells showed modal values in the "triploid" region. The analogous 71 flow-cytometric DNA histograms could only be evaluated in 50 cases because of excessively high amounts of background and/or excessively broad peaks. In 47 cases, the nuclear DNA histogram was nondiploid according to both techniques. The patients with carcinomas whose cell nuclei showed a triploid DNA distribution showed a significantly shorter survival time than those with tumor cell populations of nontriploid DNA distribution patterns. In the 8 specimens of chronic pancreatitis, the parenchymal cells were all equipped with nuclei showing diploid DNA distribution patterns.

Growth effects of regulatory peptides on human pancreatic cancer lines PANC-1 and MIA PaCa-2.

Several studies have reported effects of gastrointestinal regulatory peptides on growth of experimentally induced pancreatic neoplasms and human cancer cell lines. The growth of human pancreatic cancer lines PANC-1 and MIA PaCa-2 was characterized in vitro, and the effects of cholecystokinin, bombesin, insulin, epidermal growth factor, secretin, vasoactive intestinal peptide, and somatostatin were determined. Fetal bovine serum was required for initiation of growth in both cell lines. Growth effects of peptides were determined by incubating cells with peptides in serum-free medium after a 72-h preincubation in 10% serum-supplemented medium alone. Epidermal growth factor (3.4 x 10(-9) M) and insulin (10(-6) M) significantly (p less than 0.001) increased growth of both cell lines as determined by increases in deoxyribonucleic acid and protein. Bombesin, secretin, vasoactive intestinal peptide, and somatostatin (all 10(-8) M) did not affect growth of either cell line. Neither cholecystokinin-8 nor [Thr4, Nle7] cholecystokinin-9 altered growth in concentrations from 10(-12)-10(-6) M. Anchorage-dependent clonogenic growth of both cell lines was also not altered by cholecystokinin-8. Cholecystokinin added to cultures was degraded by separate effects of serum and cells. Addition of cholecystokinin-8 to cultures every 8 h maintained cholecystokinin levels but did not alter cell growth. These data support roles for epidermal growth factor and insulin as growth factors for human pancreatic cancer cell lines.

Regression of nitrosamine-induced pancreatic cancers in hamsters treated with luteinizing hormone-releasing hormone antagonists or agonists.

Groups of 15 female Syrian golden hamsters with N-nitrosobis(2-oxopropyl)amine-induced pancreatic cancers were treated for 2 mo with microcapsules of the luteinizing hormone-releasing hormone (LH-RH) antagonist [Ac-D-Nal(2)1-D-Phe(4Cl)2-D-Pal(3)3,D-Cit6,D-Ala10] LH-RH (SB-75) releasing 8 micrograms/day or with the microcapsules of the LH-RH agonist D-tryptophan-6-luteinizing hormone-releasing hormone (D-Trp-6-LH-RH) releasing 8 micrograms/day or 25 micrograms/day. Chronic treatment with SB-75 resulted in 70% inhibition of pancreatic tumor weight; D-Trp-6-LH-RH in doses of 8 micrograms/day and 25 micrograms/day produced 66% and 62% inhibition, respectively. The number of animals with pancreatic tumors was reduced by about 50% in each treated group. Tumorous ascites were found in seven control hamsters and in one hamster in each group treated with D-Trp-6-LH-RH but not in the group given SB-75. Reduction in serum luteinizing hormone levels and ovarian as well as uterine weights indicated that an inhibition of the pituitary-gonadal axis occurred during chronic SB-75 and D-Trp-6-LH-RH treatment. Membrane receptor assays showed a significant decrease of the concentration of binding sites for LH-RH in tumor cells after SB-75 or D-Trp-6-LH-RH treatment. Insulin-like growth factor I receptors, but not epidermal growth factor receptors, were down-regulated by D-Trp-6-LH-RH. SB-75 did not influence the concentration or the binding capacity of insulin-like growth factor I and epidermal growth factor receptors in the tumor cells. The inhibitory effect of chronic treatment with SB-75 and D-Trp-6-LH-RH on tumor growth was mediated by enhanced apoptosis (programmed cell death) induced by the change in hormonal environment. Apoptosis was also produced in hamsters with N-nitrosobis(2-oxopropyl)amine-induced pancreatic cancers by acute treatment (3 to 6 days) with high doses of D-Trp-6-LH-RH or SB-75. In view of its potency and an immediate powerful inhibitory effect, the LH-RH antagonist SB-75 might be considered as a possible new hormonal agent for the treatment of exocrine pancreatic cancer.

Rectal carcinoid tumor metastasizing to the thyroid and pancreas. An autopsy case exploiting immunohistochemistry for differentiation from tumors involving multiple endocrine organs.

A 58-year-old male patient with rectal carcinoid tumor is presented. The tumor extensively involved the lymph nodes and liver, and multiple tumors were also recognized in the pancreas and thyroid. Grossly, it was uncertain whether the latter were metastases from the rectal carcinoid or all were coincident primary tumors involving multiple endocrine organs, so-called multiple endocrine neoplasia (MEN) syndrome. Histologic, histochemical and electron microscopic examinations of the tumors in both the pancreas and thyroid showed similar features to those of the rectal carcinoid. The neoplastic cells in all involved organs commonly expressed positive immunoreactivity for somatostatin, but negativity for carcinoembryonic antigen, calcitonin, calcitonin gene-related peptide, thyroglobulin, insulin, glucagon and pancreatic polypeptide. These immunohistochemical results confirmed that the tumors observed in multiple endocrine organs were indeed metastatic from the rectal carcinoid, rather than being a new combination of MEN syndrome. Some neuroendocrine tumors may develop widespread metastasis, sometimes creating problems with differentiation from multiple primary endocrine tumors. Immunohistochemistry may be of great help in setting this issue.

Molecular and cellular analysis of a neoplastic pancreatic A cell tumor.

Endocrine tumors of the pancreas may produce characteristic syndromes attributable to the increased secretion of one or more hormones. These tumors provide valuable opportunities for the analysis of hormone biosynthesis and secretion in the neoplastic human endocrine cell. The authors studied a pancreatic endocrine tumor obtained from a patient with classical glucagonoma syndrome. Characterization of plasma and tumor glucagon-like immunoreactivity (GLI) by high-performance liquid chromatography and radioimmunoassay for GLI showed different chromatographic profiles, with glucagon the major molecular form in the tumor, and glicentin and oxyntomodulin predominating in plasma. Although immunocytochemical staining of the tumor showed only focal weak positivity for glucagon, tumor extracts contained large amounts of immunoreactive GLI peptide. Northern blot analysis of tumor RNA demonstrated that abundant glucagon mRNA transcripts were present, just slightly larger in size than those detected in normal pancreas and intestine. Electron microscopic analysis of the tumor cellular ultrastructure revealed only occasional small electron dense secretory granules. A large number of complex lysosome-like structures of variable size and electron density were detected throughout the cytoplasm and ringing the nucleus of most cells, a feature atypical of endocrine tumors of the pancreas. Primary cultures of dispersed tumor cells were established and, in contrast to previous results, were obtained using normal or neoplastic islet cell models, GLI secretion was found to be stimulated eightfold by incubation with 5 mM dibutyryl cyclic adenosine monophosphate. Phorbol myristate acetate, the calcium ionophore A23187, and sodium butyrate had no effect on GLI secretion in vitro. These observations indicate that neoplastic human A cells may have abnormalities at different points in the biosynthesis and secretion of glucagon.

Pancreatic microcystic adenoma coexistent with pancreatic ductal carcinoma. A report of two cases.

We report two cases of microcystic (glycogen-rich) adenoma of the pancreas with coexistent pancreatic adenocarcinoma. Both patients presented with an epigastric mass. On laparotomy, each had two separate pancreatic tumors. The benign tumors were composed of small cysts with a flattened to cuboidal glycogen-rich epithelium. Both malignant tumors were composed of mucinous epithelium and showed positive staining for CEA and Leu-M1. Although pancreatic microcystic adenoma and ductal adenocarcinoma are believed to arise from different precursor cells, the association reported here suggests a common predisposition to both tumors. Careful examination of the pancreas is warranted in cases of microcystic adenoma to rule out a possible coexistent pancreatic carcinoma.

[Gastrinoma and carcinoma-carcinoid tumor causing Zollinger-Ellison syndrome]. / Zollinger-Ellison-szindrómát okozó gastrinomák és carcinoma-carcinoid tumor.

7 gastrinomes and 1 gastrin-producer complex carcinoma-carcinoid tumor were examined by light and electron microscopical-method and by immunohistochemical method. In six cases, the tumor was in the pancreas or in the wall of duodenum; in two cases its localisation was of extra-gastroenteropancreatic (liver, lymph node). All patients developed Zollinger-Ellison syndrome, three patients bled and one had diarrhea. One patient had other tumors, besides gastrinome, which were characteristic of MEN-I syndrome. By immunohistochemical methods all tumors proved to be gastrin and neuron-specific-enolase positive. In four cases somatostatin positivity, in some cases glucagon, pancreatic polypeptide, S-100 protein, keratin and carcinoembryonal antigen positivity were detected. Relation could not be detected between other polypeptide hormones, produced besides gastrin, and biological behaviour of tumor and clinical symptoms.

Clinical significance of nuclear DNA content in pancreatic carcinoma.

The nuclear DNA content of 62 pancreatic adenocarcinomas was analysed by flow cytometry from paraffin-embedded material. Radical surgery could be performed in 12 of the 24 cases with diploid carcinoma, but only in 3 of the 38 cases with a non-diploid tumour (P = 0.0002); the radically resected carcinomas also had a lower fraction of cells in the S-phase (P = 0.009). Non-diploid nuclear DNA content (38 cases, 61 per cent) was associated with advanced stage (P = 0.002), poor histological differentiation (grade II or III, P = 0.004), and primary tumour site in the body or the tail as compared with the head (P = 0.01). The median survival time of the patients with diploid carcinoma was 13 +/- 3 (SE) months, and that of the patients with non-diploid carcinoma 3 +/- 1 months (P = 0.0001). The DNA index with the cutoff value 1.4 was a slightly more powerful prognostic factor than DNA ploidy, and it was the most important independent prognostic factor in Cox's multivariate analysis (P less than 0.001) followed by histological grade (P less than 0.03). We conclude that diploid pancreatic carcinomas are associated with a longer survival than the non-diploid ones, and that radically operable carcinomas form a special subgroup with frequent diploidy and less aggressive biological behaviour.

[Vasoactive intestinal peptide receptor in a human pancreatic carcinoma cell line].

Vasoactive intestinal peptide (VIP) receptors were identified in a human pancreatic carcinoma cell line by radioreceptor assay, including time course, dissociation study, competitive inhibition, and cross reactions with secretin and glucagon, both of which are hormones of the same family. Peak binding of 125I-VIP to the cells occurred at 20-30 min at 37 degrees C. Displacement curve showed an increasing inhibition of binding with increasing concentration of unlabeled VIP(inhibited by 95% at 1 microM of VIP). KD of VIP receptors was 1.68 x 10(-10)M, and the number of binding sites was 3.6 x 10(5)/cell. It was also shown that VIP was able to induce cAMP production in this cell line, indicating that the VIP receptors in this cell line were biologically active.

Neurofilament and chromogranin expression in normal and neoplastic neuroendocrine cells of the human gastrointestinal tract and pancreas.

To differentiate neuroendocrine (NE) neoplasms arising at different levels of the gut and pancreas, the authors studied the expression of neurofilament (NF) proteins and chromogranin (CR) in normal and neoplastic NE cells of the human gastrointestinal tract (GIT) (14 ileal/jejunal carcinoids, six appendiceal carcinoids, 11 rectal carcinoids) and pancreas (23 islet cell tumors). Among pancreatic islet cell tumors, those with middle molecular weight (NF-M)-positive cells were more abundant than those with high molecular weight (NF-H)-positive cells; nearly all of these tumors expressed CR. Although NF-M was abundantly expressed in greater than 50% of tumor cells in a subset of these tumors, only one of these tumors exhibited diffuse immunoreactivity with NF-H. Among rectal carcinoid tumors, NF-M and NF-H-positive cells were present in approximately the same number of tumors, yet only diffuse immunoreactivity to NF-H could be detected. Chromogranin immunoreactivity in greater than 50% of tumor cells was present in 74% of islet cell tumors, 93% of ileojejunal carcinoids, and 83% of appendiceal carcinoids, but only in a minority of rectal carcinoids (36%). Although ileojejunal carcinoid tumors rarely expressed NF-M and did not express NF-H, diffuse immunoreactivity with CR was present in nearly all of these tumors. None of the appendiceal carcinoid tumors expressed NF-M or NF-H, yet all of these tumors demonstrated immunoreactivity with CR. Neurofilament immunoreactivity was not detected in normal GIT and pancreatic NE cells, whereas CR immunoreactivity was always present. These results suggest that for NE neoplasms of the GIT and pancreas the differential expression of NF subtypes appears to be related to tumor site; and CR is a marker of most GIT and pancreatic NE neoplasms although NF may discriminate subtypes of GIT and pancreatic NE tumors. Neurofilament subtyping may be useful in the evaluation of the origin of NE tumors presenting as metastatic lesions.

Evaluation of receptors for somatostatin in various tumors using different analogs.

The binding characteristics of several somatostatin (SS-14) analogs developed in our laboratory were examined in various human and animal tumors and normal tissues. In rat cerebral cortex and human breast cancer membranes the interaction of SS-14 with its binding sites was rapid, specific, saturable, linear with protein concentrations, and dependent on time and temperature. Analysis of kinetic and equilibrium experimental data showed that the interaction of [125I-Tyr11]SS-14 with the binding sites in all normal and tumoral tissue specimens was consistent with the presence of a single class of noncooperative binding sites. Superactive octapeptide analogs of somatostatin-containing hexapeptide sequences Cys-Phe-D-Trp-Lys-Thr-Cys or Cys-Tyr-D-Trp-Lys-Val-Cys showed significant binding affinities to SS-14 receptors. Among these analogs, D-Trp-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-NH2 (RC-98-I) showed the highest binding affinity to normal human pancreatic tissue and human pancreatic adenocarcinoma. In contrast, Sandostatin (SMS 201-995) bound only to normal pancreas, not to human pancreatic cancers. Analog RC-98-I also showed a high binding to human and rat prostate cancers. In human epithelial ovarian cancers and an arrhenoblastoma, analogs D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Trp-NH2 (RC-95-I), D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2 (RC-121) and D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2 (RC-160) appeared to be the most potent in displacing labeled SS-14. Analogs Ac-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-NH2 (RC-101-I) as well as RC-121, RC-160, and RC-95-I, but not SMS-201-995, showed high binding affinity in human breast cancers. In specimens of human meningioma the highest binding was found with analogs RC-121, RC-95-I, and RC-101-I. Since marked variations in binding affinities were noted for several analogs in the tissues of origin and the tumors, this suggest that differences may exist between somatostatin receptors not only in normal vs. cancerous tissues, but also among various tumors. Our findings also imply that some analogs could be therapeutically superior to others in the treatment of certain tumors.

[Establishment of monoclonal antibodies against purified mucin from human pancreatic cell line].

Thirty four murine monoclonal antibodies were produced against mucin which was isolated from nude mouse xenografts of the SW1990 pancreatic adenocarcinoma cell line. Twelve of them reacted with formalin-fixed SW1990 cells. The antigenic determinants of these antibodies were composed of carbohydrates and their immunoreactivities were predominant at CsCl fraction #6. The remaining 22 antibodies did not react with formalin-fixed cells, 5 epitope specificities of which antibodies are present in the polypeptide part or the part of linkage between oligosaccharide and polypeptide and the immunoreactivities were predominant at CsCl fraction #5. Immunohistochemical study showed that the incidence of epitope expression of the latter 22 antibodies were higher in pancreatic cancer tissues and lower in normal pancreatic tissues than that of the former 12 antibodies. The incidence of Nd2 (one of the 22 antibodies) expression was highest in pancreatic cancer tissues and lowest in normal tissues. ELISA showed that Nd2 antigen was non-secreting type. In vivo tumor distribution studies showed that Nd2 antibody tended to accumulate in cancer tissues. These results seem to support the clinical availability of Nd2.

[Sex steroid hormone receptors in cancer of the pancreas]. / Retseptory polovykh steroidnykh gormonov pri rake podzheludochnoi zhelezy.

Samples of tumor tissue from 11 patients with pancreatic carcinoma were studied for cytoplasmic receptors of androgens and estrogens. Androgen receptors were identified in most tumors suggesting hormone-dependent nature of pancreatic cancer. Application of antiandrogens for pancreatic cancer treatment is discussed.

Papillary-cystic neoplasm of the pancreas. A clinicopathologic study concerning the tumor aging and malignancy of nine cases.

Nine female patients with papillary-cystic neoplasms (PCN) of the pancreas were studied clinicopathologically. The ages of seven of these patients ranged from 8 to 24 years. The remaining two patients, who were 47 and 60 years of age, were considered to have had the onset in their youth. There were few subjective symptoms, and the lesion was most often detected as a palpation of a mass by the patients themselves. Although the prognosis was generally favorable, the two older patients died of metastases. This suggested low-grade malignancy of PCN. The tumors were large (6.9 cm in mean diameter) and encapsulated, and their cross-sections showed an intermingling of solid tumoral areas and cystic necrotic areas. The histologic features of the solid tumoral portion were relatively uniform, with the tumor cells showing solid and pseudopapillary or pseudoglandular proliferation but few mitoses or atypism. Histochemical, immunohistochemical, and electron microscopic examinations showed polymorphic differentiation, which means that part of the tumor cells differentiated into duct epithelium, acinus, and endocrine cells (primary constituents of the pancreas). These findings suggest that the origin of PCN is totipotential primordial cells found in the development of the embryonic pancreas.

Solid-cystic tumour of the pancreas. An endocrine neoplasm?

Immunohistochemical studies and DNA flow-cytometric investigations were performed in a case of solid-cystic tumour of the pancreas in a 35-year-old woman. All tumour cells were immunoreactive for the neuroendocrine cell markers chromogranin A and neuron-specific gamma-enolase. Moreover, about 10% of tumour cells were immunoreactive for insulin, while hypoglycaemia was absent. Few tumour cells (less than 1%) were immunoreactive for somatostatin, and no cells were found to be immunoreactive for pancreatic polypeptide or glucagon. No immunoreactivity was present for duct cell marker carcino-embryonic antigen and only individual cells were reactive for alpha 1-antitrypsin. Nuclear DNA content of the tumour cells was diploid and the proliferative activity was low. In confirmation of some reports on neuroendocrine markers in solid-cystic tumour of the pancreas, our findings support the theory that the lesion is a hormonally inactive neuroendocrine pancreatic tumour.