Expression of insulin-like growth factor-1 receptor in human colorectal cancer.

The activation of the insulinlike growth factor 1/IGF-1 receptor system (IGF1/IGF1-R) has recently emerged as critical event in transformation and tumorigenicity of several murine and human tumors. Expression of IGF1 and of IGF1-R has been demonstrated in normal and neoplastic intestinal cell lines of rats and humans. However, the modulation of IGF1-R expression during the progression from normal colonic mucosa to adenoma, to carcinoma, and to metastasis, has not been evaluated. In this retrospective study, we investigated the expression of IGF1-R in 12 colonic adenomas (AD), 36 primary colorectal adenocarcinomas (CA), and in 27 corresponding metastases (MT). Normal colonic mucosa (N) was adjacent to the CA in 34 cases. Formalin-fixed, paraffin-embedded tissues of each case were immunostained using the avidin-biotin-peroxidase method. We used an anti-IGF1-R rabbit polyclonal antibody (Santa Cruz Biotechnology, CA; dilution 1:100). Positive staining was quantitated by CAS-200. Moderate to strong cytoplasmic immunostaining was observed in 34 of 36 CA (96%), and in 25 of 27 MT (93%). In all of the positive MTs, the intensity of the staining was always strong. In 10 of 12 ADs (83%), only a faint cytoplasmic stain was identified. Normal mucosa when present was negative. Strong IGF1-R positivity correlated with higher grade and higher-stage tumors (P < .01). These data suggest a role of IGF1-R expression during the progression of colorectal adenoma to carcinoma. An increased number of IGF1-R receptors may favor the metastasis of colorectal cancer.     

Modification of insulin-like growth factor 1 receptor, c-Src, and Bcl-XL protein expression during the progression of Barrett's neoplasia

Oncogenes, growth factors, cell surface receptors, and cell-cycle and apoptotic regulatory proteins have been implicated in the growth regulation and progression of Barrett's-associated neoplasia. Among these, insulin-like growth factor 1 receptor (IGF1-R) and c-Src are reported to be key regulators of mitogenesis and tumorigenesis. In addition, c-Src may exert its transforming capability by inducing increased expression of IGF1-R on the neoplastic cells. Bcl-X(L), a member of the Bcl-2 family, blocks apoptosis and has been reported to increase in Barrett's-associated neoplasia. To study the modifications in IGF1-R, c-Src, and Bcl-X(L) protein expression during the progression of Barrett's-associated neoplasia, we analyzed 34 resected gastroesophagectomy specimens by immunohistochemistry using antibodies to human IGF1-R, c-Src, and Bcl-X(L). In these cases, we found 22 intestinal (Barrett's) metaplasias (IMs), 25 low-grade dysplasias (LGDs), 28 high-grade dysplasias (HGDs), 34 invasive adenocarcinomas (CAs), and 19 lymph node metastases. High IGF1-R cytoplasmic staining was present in 14 of 19 (74%) node metastases, in 28 of 34 (82%) CAs, in 18 of 28 (64%) HGDs, in 13 of 25 (52%) LGDs, and in 5 of 22 (23%) IMs. Strong and diffuse c-Src expression was identified in 17 of 19 (89%) node metastases, in 29 of 34 (85%) Cas, in 26 of 28 (93%) HGDs, in 18 of 25 (72%) LGDs, and in 9 of 22 (41%) IMs. Bcl-X(L) cytoplasmic staining was evident in 12 of 19 (63%) node metastases, in 20 of 34 (59%) Cas, in 20 of 28 (71%) HGDs, in 15 of 25 (60%) LGDs, and in 6 of 22 (27%) IMs. In 11 cases, c-Src activity was measured by kinase assay and reflected the immunohistochemical results. Our data indicate that expression levels of IGF1-R, c-Src, and Bcl-X(L) proteins are coordinately elevated in Barrett's-associated neoplasia. These findings indicate important roles of these growth regulatory proteins in the malignant progression of Barrett's-associated neoplasia.     

Cell lineage specificity of newly raised monoclonal antibodies against gastric mucins in normal, metaplastic, and neoplastic human tissues and their application to pathology diagnosis

The specificity of monoclonal antibodies against gastric mucins (designated as HIK1083, PGM 36, and PGM 37) was studied immunohistochemically in normal, metaplastic, and neoplastic human tissues. These antibodies labeled class III mucin-producing cells identified by paradoxical concanavalin A staining in normal stomach, duodenum (Brunner gland), biliary tract, and main pancreatic duct; in mucinous metaplasia of pancreas and gallbladder; and in adenocarcinomas of stomach (90%), bile duct (80%), gallbladder (100%), pancreas (80%), lung (100% of goblet cell type adenocarcinomas), ovary (67% of mucinous carcinomas), and uterine cervix (100% of adenoma malignum tumors). Normal and neoplastic cells of esophagus, colon, salivary gland, kidney, endometrium, breast, prostate, and liver, as well as normal small intestine, lung, and uterine cervix, were all negative. The antibodies used should be valuable for the detection of class III mucin and class III mucin-producing cells in normal, metaplastic, and neoplastic tissues.     

恶性上皮性肿瘤中CK20的表达及其临床意义

目的　研究单克隆抗体CK2 0在恶性上皮性肿瘤和卵巢转移性腺癌组织中的表达及其意义。方法　应用S P法对鼻咽非角化性癌、乳腺浸润性导管癌、肺的鳞癌和腺癌、卵巢黏液性囊腺癌、胃腺癌和结肠直肠腺癌各组总计 6 7例和 4 1例分别进行了CK2 0和CK19检测。结果　CK2 0阳性率 :肺腺癌 1/ 7(14 3% ) ,卵巢浆液性和黏液性腺癌 3/ 12 (33 3% ) ,胃腺癌 3/ 9(33 3% ) ,结肠直肠腺癌组 2 1/ 2 2 (95 5 % ) ,其他癌组织均呈阴性。结肠直肠腺癌组组与其他各组间比较差异有显著性 (P <0 0 1)。CK19在上述 4 1例癌组织中均呈强阳性表达。结论　CK2 0表达对鉴别结肠腺癌和直肠腺癌与肺腺癌和乳腺浸润性导管癌具有高度特异性和较高的敏感性 ;CK2 0高表达对鉴别卵巢原发性腺癌与卵巢的结肠腺癌或直肠腺癌转移具有一定的意义     

Expression of alpha-methylacyl-CoA racemase (P504s) in various malignant neoplasms and normal tissues: astudy of 761 cases

Alpha-methylacyl CoA racemase (AMACR), also known as P504S, plays an important role in peroxisomal beta-oxidation of branched-chain fatty acids. It has recently been shown that AMACR is highly expressed in prostate cancer and that it may be an important diagnostic marker for prostate carcinoma. However, little is known about expression of AMACR in normal tissues and other malignant tumors. In this study, we investigated expression of AMACR in 539 malignant tumors and 222 normal human tissues of various types by immunohistochemical analysis. mRNA levels of AMACR in normal organs and in selected tumors were assessed by real time PCR. In normal tissue, high expression of AMACR mRNA was identified in liver, kidney and salivary gland, while AMACR protein was detected in liver (hepatocytes), kidney (tubular epithelial cells), lung (only bronchial epithelial cells), and gallbladder (only mucosal epithelial cells). High expression of AMACR mRNA was found in prostate, liver, and kidney cancers but rarely in stomach and bladder cancers. A high percent of adenocarcinomas arising from these organs express AMACR, including 17 of 21 (81%) of hepatocellular carcinomas and 18 of 24 (75%) of renal cell carcinomas. In addition, carcinomas arising from tissues normally not expressing AMACR were also positive for the antigen, including 17 of 18 (94%) prostate carcinomas, 9 of 29 (31%) of urothelial carcinomas, and 4 of 15 (27%) of gastric adenocarcinomas. Two hundred and fifty cases of adenocarcinomas from lung, breast, pancreas, bile duct, adrenal gland, salivary gland, ovary, thyroid and endometrium were negative or rarely positive for AMACR. Neuroendocrine carcinomas rarely expressed AMACR. Melanomas, squamous cell carcinomas, basal cell carcinomas, soft tissue tumors (including epithelioid sarcomas and synovial sarcoma), thymomas, and germ cell tumors were negative for AMACR. Our data provide important baseline information for using AMACR in clinical practice and also are valuable in furthering understanding of the pathogenic role of AMACR in malignant neoplasms.     

Y chromosome loss in esophageal carcinoma: An in situ hybridization study

Carcinoma of the esophagus shows a strong male predominance and other epidemiologic differences from cancers arising at other sites. In this study, the prevalence of Y chromosome loss in 29 carcinomas of the esophagus and 53 carcinomas arising elsewhere in the aerodigestive tract was assessed by in situ hybridization of formalin-fixed paraffin-embedded tissue sections. Absence of the Y chromosome was defined as (1) negative staining for Y in neoplastic cells with positive staining for Y in immediately adjacent nonneoplastic epithelial and stromal cells, (2) positive staining of neoplastic cells with control probes for chromosomes X and 17, and (3) similar results at different stringencies and levels of protein digestion. According to these criteria, absence of the Y chromosome was observed in 13 of 14 (93%) adenocarcinomas of the esophagus, 8 of 13 (62%) squamous cell carcinomas of the esophagus, and 5 of 53 (9%) carcinomas arising in other sites. For the neoplasms examined, Y chromosome deletion was strongly and selectively associated with carcinomas, particularly adenocarcinomas, of the esophagus (P < .0001). These findings suggest that Y chromosome loss may be pathogenetically significant in these neoplasms. © 1993 Wiley-Liss, Inc.     

Cytogenetic analysis of 63 non-small cell lung carcinomas: Recurrent chromosome alterations amid frequent and widespread genomic upheaval

A detailed cytogenetic analysis of 63 non-small cell lung carcinomas (NSCLCs) was carried out for identification of recurrent chromosomal alterations. Most specimens displayed very complex karyotypes with multiple numerical and structural changes (median number, 31). Losses of chromosomes 9 (65% of cases) and 13 (71%) were the most frequent numerical changes. Loss of the Y was often observed in tumors from males. Gain of chromosome 7 was also frequent (41%). Chromosome arms 1p, 1, 3p, 3q, 6q, 7q, 8q, 9p, 11q, 17p, and 19q were particularly prone to rearrangement. The chromosome arm most often contributing to losses was 9p (79%). Other arms that were frequently lost included 3p, 6q, 8p, 9q, 13q, 17p, 18q, 19p, 21q, 22q, and the short arm of each acrocentric chromosome. The percentage of cases with loss of 3p was significantly higher in squamous cell carcinomas (94%) than in adenocarcinomas (60%). There was also a statistically significant increase in the proportion of cases with gains of 1q, 7p, and 11q in adenocarcinomas compared to squamous cell carcinomas. Several recurrent isochromosomes and unbalanced exchanges were found. Among these was i(5p), which was observed in nine tumors, eight of which displayed adenomatous features. An i(8q) was identified in six cases, including five adenocarcinomas. Double minutes and/or homogeneously staining regions were seen in seven specimens. These data indicate that numerous chromosome alterations contribute to the pathogenesis of NSCLC and that, amid this widespread genomic disarray, recurrent abnormalities exist that could have biological and clinical implications.     

Survey of histologic specimens of human cancer for human papillomavirus types 6/11/16/18 by filter in situ hybridization

Histologic specimens (317) of genital and nongenital cancers and normal tissue were analyzed for the presence of the DNA of human papillomavirus (HPV) 6, 11, 16, and 18 by filter in situ hybridization performed on paraffin-embedded, formalin-fixed tissue (HISTOFISH). HPV DNA was found in 73 of 172 (42%) anogenital lesions and 17 of 116 (15%) nonanogenital carcinomas. No HPV DNA was found in normal mouse skin (five samples), human autopsy liver (two samples), or kidney (eight samples), or in carcinomas of the breast (three samples), bladder (five samples), or colon (nine samples). Of the nongenital tumors, HPV DNA was found in the carcinomas of the lung (2 of 5), anus (7 of 18), esophagus (9 of 39), buccal cavity (1 of 5), and larynx (5 of 50). HPV DNA was also detected in 2 of 11 histologically normal specimens of the cervix and 1 of 3 human skin lesions. The detection of HPV DNA in carcinomas of the lung, larynx, and esophagus as well as in the anogenital region confirms recent suggestions that HPV types 6, 11, 16, and 18 have a wider association with different types of cancer than previously believed. The study also shows that HISTOFISH is a useful method for detecting HPV-DNA in histologic specimens.     

Conserved antigen expression in epithelial tumors recognized by monoclonal antibody 4A9 generated against canine mammary carcinoma cells

Hybridoma-derived murine monoclonal antibodies (MoAbs) were generated by fusing P3X63-Ag8.653 myeloma cells with splenic cells from BALB/c mouse which had been immunized with viable canine mammary adenocarcinoma cells, CMT-2. Fifteen MoAbs were shown to react with immunizing cells in indirect immunofluorescence (IFA) and enzyme-linked immunosorbent (ELISA) assays. The reactivity of one IgM MoAb, designated 4A9, was evaluated. The antigen recognized by 4A9 on CMT-2 cells appeared to be localized both in cell membrane and cytoplasm against fixed and unfixed preparations by IFA. The 4A9 MoAb was found to bind with four of five canine mammary carcinoma cell lines while no binding was detected with normal fibroblastic cell lines. In vivo tissue distribution of 4A9 antigen was evaluated by indirect immunoperoxidase (IP) assay against formalin-fixed, paraffin-embedded sections of normal and neoplastic tissues. 4A9 MoAb reacted strongly to moderately with 75% of mammary carcinomas, moderately to weakly with 57% of benign mammary tumors, and strongly with squamous cell and perianal gland carcinomas (100%), interstitial cell tumors (100%), transitional cell carcinomas (43%), lung adenocarcinomas (40%), colon carcinomas (33%), and pancreatic adenocarcinomas (20%). Moderate to weak staining was detected with granulosa cell tumors (25%) and apocrine gland adenocarcinomas (50%). Strong reactivity with perianal gland carcinomas contrasted to no reactivity with perianal gland adenomas. No immunostaining was detected with a large variety and number of normal adult and fetal tissues tested; negligible and very restricted staining was observed in a few adult and fetal tissues. Normal mammary gland was negative. Since the antigen is expressed on the cell surface and in the cytoplasm of most mammary carcinoma cells and a variety of other epithelial tumor cells, the 4A9 antibody may have potential application in diagnosis and management of canine mammary cancer and a variety of other epithelial tumors.     

Sialosyl-Tn antigen. Its distribution in normal human tissues and expression in adenocarcinomas.

In normal adult human tissues, sialosyl-Tn antigen, detected by monoclonal antibody TKH2, was uniformly found in the bronchus, uterus, salivary gland, palatine tonsil, testis, stomach, duodenum, and capillary endothelium of several organs. It was also sporadically found in the small intestine, appendix, colorectum, gallbladder, urinary bladder, skin, and esophagus. The antigen was absent in the other organs. Even in the organs showing positive findings, the antigen was observed only in the limited areas. In contrast, sialosyl-Tn antigen was expressed in a large number of adenocarcinomas in many kinds of organs. It was expressed in more than one half the adenocarcinomas of the pancreas, ovary, uterus, stomach, colorectum, and gallbladder, but not in hepatocellular carcinomas, renal cell carcinomas, and papillary carcinomas of the thyroid gland. Sialosyl-Tn antigen expression also was observed in intestinal metaplasia of the stomach and in transitional mucosa adjacent to the colorectal carcinoma, which are considered to be cancer-related lesions. These results indicate that sialosyl-Tn antigen is a useful tumor marker, especially in adenocarcinomas of the mucin-producing organs, and suggest that the regulation of sialosyl-Tn antigen synthesis in adenocarcinomas is different from that in normal tissues.     

S100A9 expression is significantly linked to dedifferentiation of thyroid carcinoma

S100A9, a calcium-binding protein, is associated with myeloid cell differentiation and is expressed in some adenocarcinomas as well as in squamous epithelia and squamous cell carcinoma. In this study, we immunohistochemically investigated S100A9 expression in thyroid neoplasms. S100A9 was absent in normal follicles, follicular adenoma, and follicular and papillary carcinomas with conventional growth structures. In lesions showing a solid, trabecular, or scirrhous growth pattern, S100A9 immunoreacitivity was occasionally observed. One (5.9%) of the 17 follicular carcinomas and three (7.8%) of the 38 papillary carcinomas were regarded as positive for S100A9, but the positive cell areas always accounted for 5% or less. However, S100A9 was positive in all 19 undifferentiated carcinomas examined. Among them, the positive cell area was greater than 5% in 16 (84.2%), and greater than 25% in six (31.6%) cases. It is therefore suggested that S100A4 protein plays an important role in thyroid carcinoma dedifferentiation, and can be considered a novel characteristic of undifferentiated carcinoma.     

Are keratin proteins a better tumor marker than epithelial membrane antigen? A comparative immunohistochemical study of various paraffin-embedded neoplasms using monoclonal and polyclonal antibodies

Epithelial membrane antigen and keratin proteins represent markers of epithelial differentiation that may be detected in routine formalin-fixed, paraffin-embedded tissues. Eighty-seven neoplasms, including 48 adenocarcinomas of various types, squamous and transitional cell carcinomas, small-cell anaplastic carcinomas, carcinoid tumors, mesotheliomas, hepatomas, melanomas (metastatic), adrenal cortical carcinomas, germ cell tumors, and extramammary Paget's disease, were assessed to determine the relative effectiveness of these antigens as tumor markers. Immunoperoxidase studies were performed using monoclonal antibodies to epithelial membrane antigen and monoclonal (combined AE1 and AE3) and polyclonal (bovine muzzle keratins) antibodies to keratin proteins. In more than half the cases (50/87%), both markers yielded comparable results. However, in 29 cases (33%), keratin proteins were clearly superior to epithelial membrane antigen as a tumor cell marker. Particular discrepancies were apparent for some gastrointestinal adenocarcinomas, squamous cell carcinomas, hepatomas (hepatocellular type), spindle cell components of mesotheliomas, and carcinoid tumors. Epithelial membrane antigen represented a better marker in eight cases (9%), mainly for small-cell anaplastic carcinomas and some renal cell and pulmonary adenocarcinomas. Adrenal cortical carcinomas, melanomas, and seminomas were nonimmunoreactive for both antigens. Epithelial membrane antigen and keratin proteins represent useful complementary markers in diagnostic surgical pathology.     

Morphological heterogeneity of oral salivary gland carcinomas: a clinicopathologic study of 41 cases with long term follow-up emphasizing the overlapping spectrum of adenoid cystic carcinoma and polymorphous low-grade adenocarcinoma

We analyzed 41 oral salivary gland carcinomas from consecutive 290 salivary gland carcinoma database (14%) with emphasis on the histological spectrum and clinical outcome of adenoid cystic carcinoma (ACC) and polymorphous low-grade adenocarcinoma (PLGA). The cohort included 14 ACCs, 14 mucoepidermoid carcinomas (MECs), 8 PLGAs, 3 adenocarcinomas, not otherwise specified and 2 acinic cell carcinomas. Mean age was 48, 58 and 61 yrs for ACC, MEC and PLGA, respectively. Eight patients (19.5%) died of tumor at a mean interval of 66.5 months. ACC and PLGA showed similar mean age, gender distribution, predominant palatal localization, nodal metastasis, perineural invasion and MIB-1 index. However, ACC tended to show higher tumor stage and residual tumor (R1/R2) more frequently than PLGA, but this was statistically not significant. ACC and PLGA showed overlapping architectural patterns. However, ACCs displayed well organized basal-luminal differentiation, highlighted by CK5/CK7 immunostaining. In contrast, PLGA showed a disorganized histological and immunohistological pattern. C-Kit expression (CD117) was common in ACC, generally mirroring that of CK7 and virtually lacking in PLGA. Kaplan-Meier analysis demonstrated a similar clinical course for ACC and PLGA with 5 years survivals of 87% and 80%, respectively. Fluorescence in situ hybridization (FISH) performed on all 290 salivary carcinomas confirmed the specificity of the translocation t (11; 19) for MEC and its absence in all other carcinomas including ACC and PLGA. Our results emphasize the diversity of oral salivary gland carcinomas and the overlapping clinicopathological features of ACC and PLGA.     

Morphological and functional features of hepatic cyst epithelium in autosomal dominant polycystic kidney disease

We evaluated the morphological and functional features of hepatic cyst epithelium in adult autosomal dominant polycystic kidney disease (ADPKD). In six ADPKD patients, we investigated the morphology of cyst epithelium apical surface by scanning electron microscopy and the expression of estrogen receptors (ERs), insulin-like growth factor 1 (IGF1), IGF1 receptors (IGF1-R), growth hormone receptor, the proliferation marker proliferating cell nuclear antigen, and pAKT by immunohistochemistry and immunofluorescence. Proliferation of liver cyst-derived epithelial cells was evaluated by both MTS proliferation assay and [(3)H]thymidine incorporation into DNA. The hepatic cyst epithelium displayed heterogeneous features, being normal in small cysts (<1 cm), characterized by rare or shortened cilia in 1- to 3-cm cysts, and exhibiting the absence of both primary cilia and microvilli in large cysts (>3 cm). Cyst epithelium showed marked immunohistochemical expression of ER, growth hormone receptor, IGF1, IGF1-R, proliferating cell nuclear antigen, and pAKT. IGF1 was 10-fold more enriched in the hepatic cyst fluid than in serum. Serum-deprived liver cyst-derived epithelial cells proliferated when exposed to 17beta-estradiol and IGF1 and when exposed to human cyst fluid. ER or IGF1-R antagonists inhibited the proliferative effect of serum readmission, cyst fluid, 17beta-estradiol, and IGF1. Our findings could explain the role of estrogens in accelerating the progression of ADPKD and may suggest a potential benefit of therapeutic strategies based on estrogen antagonism.     

WT1 is an integral component of an antibody panel to distinguish pancreaticobiliary and some ovarian epithelial neoplasms

We investigated whether a panel of antibodies including WT1 could separate pancreaticobiliary and ovarian carcinomas by staining 64 pancreaticobiliary adenocarcinomas, 41 ovarian serous carcinomas, and 12 primary ovarian mucinous neoplasms with WT1, cytokeratin (CK) 17, CK20, carcinoembryonic antigen (CEA), and CA-125. Moderate or strong intensity reactivity in more than 25% of cells was a positive result. Of the ovarian serous carcinomas, 38 (93%) were WT1 reactive and 22 (54%) WT1 positive, 9 (22%) had CK20 reactivity, and 3 (7%) were CK20 positive in fewer than 50% of cells. All were CK17 or CEA nonreactive. Of the ovarian mucinous neoplasms, all were WT1 and CK17 nonreactive and 11 (92%) were CEA reactive, 8 (67%) CEA positive, 10 (83%) CK20 reactive, and 6 (50%) CK20 positive. Of the pancreaticobiliary adenocarcinomas, 19 (30%) were CK20 positive, 27 (42%) CK17 positive, and 52 (81%) CEA positive. All were WT1 nonreactive. A panel including WT1, CK17, CK20, and CEA is useful to distinguish pancreaticobiliary and ovarian serous carcinomas. Extensive CK17 reactivity is supportive of a pancreaticobiliary adenocarcinoma when the differential diagnosis includes ovarian mucinous neoplasm. None of the antibodies positively identified ovarian mucinous neoplasms.     

Overexpression of cyclin D1 occurs in both squamous carcinomas and adenocarcinomas of the esophagus and in adenocarcinomas of the stomach.

Increased expression of the cyclin D1 gene frequently occurs in human squamous carcinomas of the esophagus. However, the expression of cyclin D1 has not been previously examined in detail in adenocarcinomas of the esophagus or stomach. Therefore, we examined, in parallel, the expression of cyclin D1 in both squamous and adenocarcinomas of the esophagus and in adenocarcinomas of the stomach. The level of expression of the cyclin D1 protein was assessed by immunohistochemistry in 39 esophageal and 34 gastric carcinomas and correlated with clinical and pathology parameters. Within the esophagus, 71% of the squamous carcinomas and 64% of the adenocarcinomas were positive for increased cyclin D1 nuclear staining. For adenocarcinomas of the stomach, the overall positive rate was 47%; in the gastric cardia, the rate was 44%, and in other regions of the stomach, it was 50%. In esophageal and gastric adenocarcinomas of the intestinal type, increased expression of cyclin D1 was seen in 70% of the samples, whereas with the diffuse type only 13% were positive (P < .01). Tumors from patients older than the median age of 67 years were more frequently positive than tumors from patients younger than 67 years (74% v 42%, respectively) (P < .01). Positive staining was also seen more frequently in well and moderately differentiated tumors than in poorly differentiated tumors (74% v 49%, respectively) (P < .05). Cytoplasmic staining for cyclin D1 was noted in 22% of the tumors, of various types. Therefore, increased expression of cyclin D1 frequently occurs in both adenocarcinomas and squamous carcinomas of the esophagus, and in adenocarcinomas of the stomach. The increased expression in adenocarcinomas is especially frequent in the intestinal-type lesions.     

Immunohistochemical localization of WT1 in epithelial salivary tumors

The subcellular localization of WT1 is controversial and has received little attention in the epithelial tumors of salivary glands. Paraffin-embedded, surgical specimens from 80 salivary tumors were investigated by immunohistochemistry using a monoclonal, anti-WT1 antibody (6F-H2, Dako). Immunostaining was seen in 14/14 pleomorphic adenomas (PAs), 6/6 myoepitheliomas, 4/4 basal cell adenomas, 4/4 canalicular adenomas, 0/7 Warthin tumors, 0/1 oncocytoma, 1/6 acinic cell carcinomas (Cas), 0/11 mucoepidemoid Cas, 1/11 adenoid cystic Cas, 11/12 polymorphous low-grade adenocarcinomas (PLGAs), 1/2 Ca ex PA, 0/1 salivary duct Ca and 0/1 clear cell adenocarcinoma. Stained-cell subpopulations up to 90% were not uncommon in the benign tumors. Up to 80% of cells in PLGA could be stained. Staining was weak to intense and confined to the cytoplasm of preferentially non-luminal or adjacent to stroma cells. One adenoid cystic Ca showed nuclear staining. The results suggest that WT1 is often highly expressed in benign non-oncocytic salivary tumors whereas the malignant tumors show decreased expression, the exception being PLGA. The expression is usually cytoplasmic and associated with non-luminal cells. PLGA immunoreactivities could be useful in histological differential diagnosis.