Prostatic tissue ectopia within the seminal vesicle: a potential source of confusion with seminal vesicle involvement by prostatic adenocarcinoma.
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Adenocarcinoma↗
Biomedical subjects
Peiguo G Chu
Publications and source records attributed to Peiguo G Chu.
Production of a monoclonal antibody against the hRRM2 subunit of ribonucleotide reductase and immunohistochemistry study of human cancer tissues.
We report production of a monoclonal antibody against the hRRM2 subunit of ribonucleotide reductase and immunohistochemistry (IHC) staining of human cancer tissues available in paraffin block. BALB/c mice were immunized with purified hRRM2 protein, and splenocytes from these mice were fused with mice myeloma cell lines by using standard hybridoma production techniques. Resulting hybridomas producing anti-hRRM2 antibodies were screened by enzyme-linked immunosorbent assay (ELISA). The specificity was determined by limiting serial dilutions. Clones were chosen for antibody production based on their activities on paraffin-embedded human tissues. They were then isotyped and shown to produce immunoglobulin M (IgM) antibodies against hRRM2. Using these antibodies, we performed Western blot on oropharyngeal KB cancer cell lines and immunohistochemistry staining of available paraffin-embedded cancer tissues. Interestingly, cancer tissues stained positive with the anti-hRRM2 antibody but not normal tissues. Colon, stomach, liver, lung, pancreatic, and breast cancer had the strongest staining. No staining was identified on astrocytoma, mesothelioma, or myeloma. Our findings were validated with data from reverse transcriptase-polymerase chain reaction (RT-PCR) demonstrating overexpression of hRRM2 in breast cancer tissues compared to matched noncancer tissues. We propose that IHC with this monoclonal anti-hRRM2 antibody may be useful for ribonucleotide reductase research and as a biomarker for tumorgenesis.
Animals↗
Immunohistochemical expression of estrogen receptor in pulmonary adenocarcinoma.
Estrogen receptor (ER) is a useful immunohistochemical marker of breast carcinomas and is commonly used as a means of distinguishing breast carcinomas from adenocarcinomas of other primary sites, including the lung. Previous reports have yielded conflicting data regarding ER immunoreactivity in primary pulmonary adenocarcinomas. In this study the immunohistochemical expression of ER was evaluated in 55 primary lung adenocarcinomas using the 1D5 antibody clone. Immunohistochemistry for thyroid transcription factor-1 (TTF-1), a sensitive and specific marker of pulmonary adenocarcinomas, was also performed. ER expression was observed in 10 (18%) of 55 lung adenocarcinomas. Most of these pulmonary adenocarcinomas showed ER immunoreactivity of weak or moderate intensity (<25% of tumor cell nuclei). However, two cases exhibited strong ER immunoreactivity (51-75% of neoplastic cells). Forty-six (84%) of the 55 lung adenocarcinomas were TTF-1 positive, including all those that expressed ER. These results indicate that a subset of pulmonary adenocarcinomas can exhibit ER immunoreactivity. As such, caution should be exercised in the use of ER immunohistochemistry alone as a means of distinguishing breast carcinomas from lung adenocarcinomas. In the context of an ER-positive lung neoplasm, strong and extensive TTF-1 immunoreactivity can be regarded as strong supportive evidence for a primary bronchogenic adenocarcinoma.
Adenocarcinoma↗
Lineage determination of CD20- B-Cell neoplasms: an immunohistochemical study.
We studied 61 CD20- B-cell lymphomas, including 29 cases of precursor B-cell lymphoblastic leukemia/lymphoblastic lymphoma (B-ALL/B-LBL), 25 cases of CD20- recurrent mature B-cell lymphoma after rituximab therapy, and 7 cases of CD20- diffuse large B cell lymphoma (DLBCL). We used markers specific for B lineage: CD79a, Pax-5, OCT.2, and BOB.1. All B-ALL/B-LBLs expressed Pax-5 (29/29 [100%]), 25 (93%) of 27 expressed BOB.1, 23 (79%) of 29 expressed CD79a, and 6 (22%) of 27 expressed OCT.2. The percentages of cases expressing Pax-5, CD79a, OCT.2, and BOB.1 in CD20- recurrent mature B-cell lymphomas after rituximab treatment were 88% (21/24), 84% (21/25), 81% (17/21), and 73% (16/22), respectively. CD20- DLBCLs rarely express routine B-lineage markers, such as and CD79a and Pax-5, but they expressed OCT.2 or BOB.1. Pax-5, BOB.1, and CD79a antigens are the most reliable B-lineage markers for paraffin immunophenotyping B-ALL/B-LBL. CD79a and Pax-5 should be used as the first-line B lineage-specific markers for rituximab-treated CD20- mature B-cell lymphomas. If negative, OCT.2 or BOB.1 may be useful. The newly identified B-lineage markers, OCT.2 and BOB.1, may be the most useful for the B-lineage determination of CD20- plasmablastic or primary effusion subtypes of DLBCL.
Antibodies, Monoclonal↗
Immunohistochemical staining in the diagnosis of pancreatobiliary and ampulla of Vater adenocarcinoma: application of CDX2, CK17, MUC1, and MUC2.
Pancreatobiliary and ampulla of Vater adenocarcinomas frequently metastasize to regional lymph nodes, liver, or lung and are difficult to diagnose because they lack specific immunohistochemical markers. We studied the expression of cytokeratin 7 (CK7), cytokeratin 17 (CK17), cytokeratin 20 (CK20), CDX2, mucin 1 (MUC1), mucin 2 (MUC2), and mucin 5AC (MUC5AC) in 46 cases of pancreatic ductal carcinoma, 18 ampulla of Vater adenocarcinomas, and 24 intrahepatic cholangiocarcinomas. The expression of MUC1 and CK17 was restricted to pancreatic ductal carcinoma (41 of 46, 89%; 38 of 46, 83%, respectively), the ampullary carcinoma of pancreatobiliary origin (6 of 6, 100%; 5 of 6, 83%, respectively), and intrahepatic cholangiocarcinoma (20 of 24, 83%; 17 of 24, 71%, respectively). More than 50% of cases of pancreatobiliary adenocarcinomas showed diffuse cytoplasmic CK17 positivity. In contrast, less than 5% cases (8 of 184) of extra-pancreatobiliary nonmucinous adenocarcinomas expressed CK17, and only 3 of them showed diffuse CK17 positivity. The expression of MUC2 and CDX2 was restricted to the intestinal, mucinous, and signet-ring cell-type adenocarcinomas of duodenal papillary origin (9 of 11, 82%; 11 of 11, 100%, respectively). MUC2 was rarely expressed in pancreatic ductal carcinoma (1 of 46, 2%) and was negative in the ampullary carcinoma of pancreatobiliary origin and in intrahepatic cholangiocarcinoma. A heterogeneous CDX2 staining pattern was seen in 1 of 6 cases of the ampullary carcinoma of pancreatobiliary origin (17%), 5 of 24 intrahepatic cholangiocarcinomas (21%), and 10 of 46 (22%) pancreatic ductal carcinomas. In contrast, all 11 cases of the intestinal, mucinous, and signet-ring cell-type adenocarcinomas of duodenal papillary origin showed homogeneous CDX2 nuclear positivity. We concluded that CK17 is a useful marker in separating pancreatobiliary adenocarcinomas from extra-pancreatobiliary nonmucinous adenocarcinomas, including adenocarcinomas from the colon, breast, gynecologic organs, stomach, lung, prostate, thyroid, kidney, and adrenal gland, and malignant mesothelioma. MUC1+/CK17+ can be used as positive markers for pancreatic ductal carcinomas, the ampullary carcinoma of pancreatobiliary origin, and cholangiocarcinomas with positive predictive values of 76%, 83%, and 58%, respectively. MUC2+/CDX2+ can be used as positive markers for the intestinal-type adenocarcinoma of duodenal papillary origin with a positive predictive value of 82%.
Adenocarcinoma↗
Incidental and concurrent malignant lymphomas discovered at the time of prostatectomy and prostate biopsy: a study of 29 cases.
The incidence and histologic features of malignant lymphomas discovered at the time of prostate biopsy, transurethral resection, and prostatectomy are not well documented. We searched our surgical pathology files for malignant lymphomas identified from prostate surgical specimens from 1989 to 2004. Of 4,831 cases of prostate specimens (3,405 biopsies, 266 transurethral resections, 1,160 prostatectomies) examined at the City of Hope during this period, 29 cases of malignant lymphomas involving the prostate and pelvic lymph nodes were identified (0.6%). These malignant lymphomas can be divided into two groups: 1) 18 incidental cases (0.37%) without prior history of malignant lymphoma; and 2) 11 cases (0.23%) with concurrent known malignant lymphoma. For the first group, the patients with pelvic node involvement ranged in age from 59 to 78 years (mean, 69.2 years; median, 70 years), and the patients with prostate involvement ranged in age from 45 to 78 years (mean, 64.6 years; median, 67.5 years). For the second group, the patients ranged in age from 53 to 80 years (mean, 66.8 years; median, 69 years). Diagnoses of all cases were confirmed by immunohistochemistry or molecular analysis. Ten of 18 cases in the first group involved pelvic nodes only, and the other 8 cases were primary prostatic lymphoma. Of 18 cases in the first group, 13 were small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL), 3 were marginal zone B-cell lymphoma, and 1 was mantle cell lymphoma. These lymphomas were not readily apparent in most cases by histologic examination, and may be confused with chronic prostatitis when the prostate was involved or with reactive lymphoid hyperplasia when pelvic nodes were involved. Immunohistochemistry and molecular studies may be necessary to confirm the diagnosis. For the second group, prostate and pelvic lymph nodes were involved as part of systemic dissemination of concurrent malignant lymphoma. The diagnosis was usually easily established in these cases. Of 11 cases, 4 were SLL/CLL, 4 were follicular lymphoma, 2 were mantle cell lymphoma, and 1 was diffuse large B-cell lymphoma.
Aged↗
Paraneoplastic syndromes in cancer: Case 3. Parathyroid hormone-related hypercalcemia in cholangiocarcinoma.
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Cholangiocarcinoma↗
Bacteria-induced intestinal cancer in mice with disrupted Gpx1 and Gpx2 genes.
Two glutathione peroxidase (GPX) isozymes, GPX-1 and GPX-2 (GPX-GI), are the major enzymes that reduce hydroperoxides in intestinal epithelium. We have previously demonstrated that targeted disruption of both the Gpx1 and Gpx2 genes (GPX-DKO) results in a high incidence of ileocolitis in mice raised under conventional conditions, which include the harboring of Helicobacter species [non-specific-pathogen-free (non-SPF) conditions]. In this study, we have characterized GPX-DKO mice that have microflora-associated intestinal cancers, which are correlated with increased intestinal pathology/inflammation. We found that GPX-DKO mice raised under germ-free conditions have virtually no pathology or tumors. After colonizing germ-free mice with commensal microflora without any known pathogens (SPF), <9% of GPX-DKO mice develop tumors in the ileum or the colon. However, about one-fourth of GPX-DKO mice raised under non-SPF conditions from birth or transferred from SPF conditions at weaning have predominantly ileal tumors. Nearly 30% of tumors are cancerous; most are invasive adenocarcinomas and a few signet-ring cell carcinomas. On the basis of these results, we conclude that GPX-DKO mice are highly susceptible to bacteria-associated inflammation and cancer. The sensitivity exhibited in these mice suggests that peroxidative stress plays an important role in ileal and colonic pathology and inflammation, which can lead to tumorigenesis.
Animals↗
Urothelial carcinoma of the urinary bladder with a component of acinar/tubular type differentiation simulating prostatic adenocarcinoma.
We report a case of an 83-year-old man with a high-grade carcinoma of the urinary bladder who underwent cystoprostatectomy. The invasive carcinoma showed mixed, morphologically distinct patterns consisting of conventional high-grade urothelial carcinoma, glandular differentiation resembling enteric type adenocarcinoma, and acinar/tubular type differentiation, morphologically similar to Gleason grade 3 prostatic adenocarcinoma. Immunohistochemical studies revealed the acinar/tubular component of the tumor to be negative for prostate-specific antigen and prostatic acid phosphatase, but positive for cytokeratin 7, cytokeratin 20, high molecular weight cytokeratin (34 beta E12), and thrombomodulin, consistent with origin from the bladder rather than the prostate. Although bladder carcinomas composed of mixed morphologic patterns are not uncommon, to our knowledge, the presence of acinar/tubular type features simulating prostatic adenocarcinoma in such tumors has not been described elsewhere.
Adenocarcinoma↗
Hypermethylation of growth arrest DNA damage-inducible gene 45 beta promoter in human hepatocellular carcinoma.
Growth arrest DNA damage-inducible gene 45 beta (GADD45beta) has been known to regulate cell growth, apoptotic cell death, and cellular response to DNA damage. Down-regulation of GADD45beta has been verified to be specific in hepatocellular cancer (HCC) and consistent with the p53 mutant, and degree of malignancy of HCC. This observation was further confirmed by eight HCC cell lines and paired human normal and HCC tumor tissues by Northern blot and immunohistochemistry. To better understand the transcription regulation, we cloned and characterized the active promoter region of GADD45beta in luciferase-expressing vector. Using the luciferase assay, three nuclear factor-kappaB binding sites, one E2F-1 binding site, and one putative inhibition region were identified in the proximal promoter of GADD45beta from -865/+6. Of interest, no marked putative binding sites could be identified in the inhibition region between -520/-470, which corresponds to CpG-rich region. The demethylating agent 5-Aza-dC was used and demonstrated restoration of the GADD45beta expression in HepG2 in a dose-dependent manner. The methylation status in the promoter was further examined in one normal liver cell, eight HCC cell lines, eight HCC tissues, and five corresponding nonneoplastic liver tissues. Methylation-specific polymerase chain reaction and sequencing of the sodium bisulfite-treated DNA from HCC cell lines and HCC samples revealed a high percentage of hypermethylation of the CpG islands. Comparatively, the five nonneoplastic correspondent liver tissues demonstrated very low levels of methylation. To further understand the functional role of GADD45beta under-expression in HCC the GADD45beta cDNA constructed plasmid was transfected into HepG2 (p53 WT) and Hep3B (p53 null) cells. The transforming growth factor-beta was assayed by enzyme-linked immunosorbent assay, which revealed a decrease to 40% in transfectant of HepG2, but no significant change in Hep3B transfectant. Whereas, Hep3B co-transfected with p53 and GADD45beta demonstrated significantly reduced transforming growth factor-beta. The colony formation was further examined and revealed a decrease in HepG2-GADD45beta transfectant and Hep3B-p53/GADD45beta co-transfectant. These findings suggested that methylation might play a crucial role in the epigenetic regulation of GADD45beta in hepatocyte transformation that may be directed by p53 status. Thus, our results provided a deeper understanding of the molecular mechanism of GADD45beta down-regulation in HCC.
Apoptosis↗
Epstein-Barr virus plays no role in the tumorigenesis of small-cell carcinoma of the lung.
Epstein-Barr virus infection has been associated with lymphoepithelioma-like carcinoma of the lung in Asian patients. Recently, Epstein-Barr virus proteins or genomic DNAs were detected in pulmonary squamous-cell carcinoma, adenocarcinoma, and undifferentiated small-cell carcinoma in American patients. We studied 23 cases of small-cell carcinoma of the lung for evidence of Epstein-Barr virus infection by in situ hybridization, immunohistochemistry, and polymerase chain reaction methods. Of the 23 cases, 13 cases were primary small-cell carcinoma of the lung and 10 cases were metastatic small-cell carcinoma of the lung to the brain (one case), liver (two cases), and lymph nodes (seven cases). None of the 23 cases was positive for Epstein-Barr virus-encoded small nonpolyadenylated RNA (EBER)-1 by in situ hybridization. By immunohistochemistry, eight cases showed focal positivity for Epstein-Barr virus nuclear antigen-1. The positive immunostaining was focal and was observed in tumor cells, vascular endothelial cells, and lymphocytes, suggesting nonspecific staining. None of the 23 cases was positive for the transactivating immediate-early BZLF1 (ZEBRA) and latent membrane protein (LMP-1). Only one case was positive for the BamHI W region and LMP-1 gene by polymerase chain reaction assay. Some tumor cells in the BamHI W region positive case were also positive for Epstein-Barr virus nuclear antigen-1. Our study indicates that rare cases of American small-cell carcinoma of the lung may contain Epstein-Barr virus-infected cells, but it is unlikely that Epstein-Barr virus plays a role in the tumorigenesis of small-cell carcinoma of the lung.
Biomarkers, Tumor↗
Intraneural synovial sarcoma: two cases.
We report two cases of intraneural synovial sarcoma. The first patient is a 46-year-old female who presented for several months with soft-tissue mass in the right infra-auricular region. The second patient is a 11-year-old girl who fell and then presented with pain in the area innervated by the right C7 spinal root and a nodule identified in the nerve root foramina. Both lesions were of small size and presented with features of synovial sarcoma. A biphasic variant was found in case 1 and a monophasic variant was present in case 2. Immunohistochemical studies were performed to confirm the diagnosis, excluding the main differential diagnoses, namely schwannoma and malignant peripheral nerve sheath tumor. Ultrastructural study was performed in case 2 allowing exclusion of other possible diagnoses. Molecular studies were performed on paraffin-embedded tissue in both cases and revealed the known characteristic t(X;18)(SYT-SSX) translocation.
Child↗
Pancreatic tumors in patients with lung malignancies: a spectrum of clinicopathologic considerations.
OBJECTIVES: Lung cancer and pancreatic cancer are the most lethal tobacco-associated malignancies. To elucidate possible clinical interrelationships, the authors reviewed the clinicopathologic characteristics of patients treated for both pulmonary and pancreatic neoplasms. METHODS: Patients presenting with a potentially resectable pancreatic mass and a diagnosis of metachronous malignant neoplasm of the lung were studied by retrospective chart audit and review of histopathologic material. RESULTS: Seven patients were identified over 6 years, representing five different clinical entities: metachronous presence of lung cancer and pancreatic cancer (n = 3), lung cancer metastatic to the pancreas (n = 1), lung cancer with a benign pancreatic neoplasm (n = 1), periampullary cancer metastatic to the lung (n = 1), and malignant melanoma metastatic to both lung and pancreas (n = 1). A tobacco history was present in all patients but one. Primary treatment modality was complete resection of isolated sites whenever feasible (lung resection, n = 6; pancreatic resection, n = 5). In four cases, a differential diagnosis of adenocarcinomas of both lung and pancreas was obtained after cytokeratin (CK) 7 and CK 20 immunohistochemistry. All patients with evidence of nodal or visceral metastasis from either primary site (n = 4) died within 5 to 9 months after the last operation. Three of four patients who had undergone resection of both pulmonary and pancreatic tumors were alive between 17 and 67 months after the last operation. All three survivors had presented with early disease stages and/or a protracted course (diagnostic interval, 16-66 months). CONCLUSIONS: Our experience with neoplastic conditions that can involve lungs and pancreas metachronously may be useful to the clinician who is confronted with a similar situation. If therapeutic decision-making depends on differential diagnostic analysis, examination of CK 20 expression appears to be helpful. Although biologically favorable circumstances are rarely present, long-term survival seems possible after complete operative treatment in selected patients with early-stage disease.
Adenocarcinoma↗
Differential expression of MUC1, MUC2, and MUC5AC in carcinomas of various sites: an immunohistochemical study.
We studied immunohistochemical expression of MUC1, MUC2, and MUC5AC in 194 carcinomas of different primary sites to determine whether differential expression patterns could be used to distinguish different carcinomas. MUC1 was expressed by most (except adrenocortical and hepatocellular carcinomas). MUC2 was expressed infrequently (positive immunoreactivity primarily in tumors of gastrointestinal origin). MUC5AC was expressed by most pancreatic ductal and endocervical adenocarcinomas and a variable number of tumors of the gastrointestinal tract. A MUC1+/MUC2-/MUC5AC- immunophenotype was observed in most breast, lung, kidney, bladder, endometrial, and ovarian carcinomas; MUC1+/MUC2-/MUC5AC+ was characteristic of pancreatic ductal adenocarcinomas and cholangiocarcinomas. Adrenocortical and hepatocellular carcinomas were negative for all mucins. Carcinomas of gastrointestinal origin exhibited variable expression of each mucin examined and no consistent immunoreactivity pattern. Many carcinomas can exhibit distinct MUC1, MUC2, and MUC5AC expression patterns, which might be valuable diagnostically in specific settings (eg, distinguishing cholangiocarcinoma from hepatocellular carcinoma or renal from adrenocortical carcinoma). However the overlapping and heterogeneous patterns of MUC1, MUC2, and MUC5AC expression observed in many tumors, particularly those of gastrointestinal origin, preclude use of these markers in the routine immunohistochemical assessment of carcinomas of an unknown primary site.
Biomarkers, Tumor↗
Immunohistochemical characterization of signet-ring cell carcinomas of the stomach, breast, and colon.
We studied the immunophenotype of signet-ring cell carcinoma (SRCC) of the stomach (30 cases), breast (21 cases), and colon (9 cases) with the following expression patterns: (1) breast: consistent, MUC1 (21 [100%]), cytokeratin (CK) 7 (20 [95%]), estrogen receptor (ER; 17 [81%]); infrequent, E-cadherin (6 [29%]), MUC2, MUC5AC, CK20 (1 [5%] each); negative, CDX2 and hepatocyte paraffin 1 (Hep Par 1; 0 [0%] each); (2) gastric: frequent, CDX2 (27 [90%]) and Hep Par 1 (25 [83%]); variable, E-cadherin and CK20 (17 [57%] each), MUC2 and MUC5AC (15 [50%] each), MUC1 (5 [17%]); negative, ER (0 [0%]); and (3) colon: frequent, MUC2 (9 [100%]), CDX2 and MUC5AC (8 [89%] each); infrequent or negative, MUC1 (3 [33%]), Hep Par 1 (2 [22%]), ER (0 [0%]). Immunohistochemical staining distinguished breast from gastric SRCC (ER, MUC1, Hep Par 1, CDX2) and colon SRCC (ER, CDX2, MUC2, and MUC5AC). Gastric and colon SRCCs showed a similar staining pattern for antibodies tested except for Hep Par 1 and CDX2 (gastric, 83% Hep Par 1 positivity and heterogeneous, weak, patchy CDX2 nuclear staining; colon, 22% Hep Par 1 positivity and homogeneous, strong, diffuse CDX2 nuclear staining). About half of the cases of gastric SRCC expressed MUC2 and MUC5AC, whereas virtually all cases of colon SRCC expressed them.
Biomarkers, Tumor↗
CD163: a specific marker of macrophages in paraffin-embedded tissue samples.
Paraffin-section immunohistochemical analysis was performed using a monoclonal antibody against CD163 to evaluate the antibody's usefulness in identifying cells of monocyte/macrophage lineage in normal and neoplastic conditions. Normal human tissue samples and samples from 211 hematopoietic disorders and 115 nonhematopoietic neoplasms were examined. The distribution of KP1 and PG-M1, monoclonal antibodies to the macrophage-associated CD68 antigen, also were evaluated for comparison. CD163 immunoreactivity was observed in resident macrophages of all normal tissue samples except splenic white pulp macrophages and germinal center tingible body macrophages. Among hematopoietic disorders and nonhematopoietic neoplasms, CD163 expression was restricted largely to cases of chronic myelomonocytic leukemia, histiocytic sarcoma, sinus histiocytosis with massive lymphadenopathy, and littoral cell angioma. Acute myeloid leukemias (AMLs) with monocytic differentiation were CD163- with the exception of 1 case of acute monoblastic leukemia. Most myeloid sarcomas also were CD163-. Compared with the CD68 antibodies, CD163 demonstrated greater specificity as a marker of disorders of monocyte/macrophage origin. However, immunohistochemical evaluation of CD163 expression does not seem to be a sensitive means of determining monocytic differentiation in AMLs in paraffin sections or establishing a diagnosis of myeloid sarcoma.
Antigens, CD↗
A dietary enzyme: alpha-methylacyl-CoA racemase/P504S is overexpressed in colon carcinoma.
Epidemiological studies have shown that consumption of red meat increases the risk of developing colon cancer. An enzyme, alpha-methylacyl CoA racemase (AMACR), also known as P504S, plays an important role in peroxisomal beta-oxidation of branched-chain fatty acids from red meat and dairy products. High expression of AMACR was recently found in prostate cancer. In this study, we investigated expression of AMACR in 242 cases of colonic tumors including 176 colorectal carcinomas, 38 colon adenomas and 28 hyperplastic (non-neoplastic) polyps by immunohistochemical analysis. The mRNA levels of AMACR expression in normal and colon cancer tissues were assessed by real-time PCR. Significant up-regulation of AMACR mRNA was found in colon carcinomas compared to normal tissue. There was very low or no expression of AMACR protein in normal colon, but AMACR was highly expressed in 76 and 75% of well and moderately differentiated colon carcinomas, respectively, and in 79% of adenomas. In contrast, only 4% of hyperplastic polyps expressed AMACR. Since this enzyme is involved in the metabolism of branched-chain fatty acids from beef, milk and dairy products, our results provide important molecular information regarding a possible link between diet and development of colon cancer. AMACR may also serve as a molecular marker for colon cancers and its precursor lesions.
Adenocarcinoma↗
Down-regulation of growth arrest DNA damage-inducible gene 45beta expression is associated with human hepatocellular carcinoma.
In this study, we describe the growth arrest DNA damage-inducible gene 45beta (GADD45beta), whose expression was significantly down-regulated in the hepatocellular carcinoma (HCC) microarray study and confirmed by Northern blot analysis. The results suggested that expression of GADD45beta was decreased in human liver cancer cell lines HepG2 and Hep3B, but not in normal human embryonic liver cell line CL-48 or normal liver tissue. Histochemistry study and real-time PCR further confirmed that GADD45beta staining in HCC was significantly decreased when compared to surrounding non-neoplastic liver tissue. In further studies of multiple human cancer tissues, GADD45beta strongly stained tissues such as colon cancer, breast cancer, prostate cancer, squamous cell cancer, lymphoma, and leiomyosarcoma, suggesting that the decreased expression of GADD45beta is specific to HCC. Eighty-five cases of primary HCC were further examined by immunohistochemistry and statistical analyses demonstrated that HCC scored lower than matched non-neoplastic liver tissues consistently and significantly. No staining occurred in 12.94% of HCC cases (score = 0, n = 11); 42.35% had weak staining (score = 1, n = 36); 27.06% had moderate staining (score = 2, n = 23); and 17.65% had staining as strong as normal tissue (score = 3, n = 15). Overall, surrounding non-neoplastic liver tissue was highly positive for GADD45beta compared to adjacent neoplastic liver tissues (P < 0.01). We further observed that down-regulation of GADD45beta expression was strongly correlated with differentiation (P < 0.01) and high nuclear grade (P < 0.01). Moreover, we found that expression of GADD45beta was inversely correlated to the presence of mutant p53 in HCC tissue (P < 0.05). Thus, the results of our study suggest that GADD45beta, which is down-regulated in most cases of HCC, remains an ideal candidate for development as a molecular marker in the diagnosis of HCC and as a potential therapeutic target.
Adult↗