Dataset Information

CAN IMMUNOHISTOCHEMISTRY DISTINGUISH BETWEEN PRIMARY AND METASTATIC HEPATIC CARCINOMA?

ABSTRACT: To determine if immunohistochemistry is useful to distinguish between primary and metastatic hepatic carcinoma.Cases of hepatocellular and adenocarcinoma of liver from surgical and autopsy pathology files as diagnosed on routine histopathology with the help of haematoxylin-eosin stain.Thirty four patients with hepatic space - occupying lesions (a single lesion in 6 patients, multiple lesions in 5 patients and unspecified in remaining 23 patients). The histopathology diagnosis included 14 hepatocellular carcinoma (HC), 10 cholangiocarcinoma (CC), 7 metastatic carcinoma (MC) (colonic: n=4, pancreatic: n=2, mammary: n=l) and three cases were unclassified.The paraffin embedded blocks of biopsy and autopsy cases were taken out and sections of 4 µm thickness were cut. The immunohistochemistry staining was carried out by using a panel of 7 monoclonal antibodies. The monoclonal antibodies which were used were as follows - a fetoprotein (AFP), α 1 antitrypsin (AAT), monoclonal carcinoembryonic antigen (MCEA), myelomonocytic antigen (Leu-Ml), tumour associated glycoprotein (B72-3), A-subunit coagulation Factor XIII (Factor XIIIa) and blood group substance (Lex).Sections were defined as immunohistochemically 'positive' if definitive crisp labelling was seen in atleast 10% of tumour cells by two observers. The positive staining was classified as either predominantly cytoplasmic or membranous or both. The presence or absence of nuclear staining was also noted.The typical immunoreactivity of HCs included positivity for AAT, AFP and factor XIIIa and no staining for B 72-3 and Leu-Ml. Of 14 patients who were originally diagnosed as having HC, AAT was expressed in 86% and AFP was expressed in cytoplasm in half of the patients. Factor XIIIa displayed cytoplasmic reactivity in 71% cases of HC. Lex was present focally in 3 cases of HC, as was monoclonal CEA. These 3 cases showed features of hepatocholangiocarcinoma. In all 10 cases of CC there was staining for both Leu-Ml and Lex. The pattern of reactivity was cytoplasmic for Leu-Ml and it was both cytoplasmic and membranous for Lex. In 6 cases there was expression of B72-3 and monoclonal CEA in cytoplasm. None of the cases of CC showed staining for AFP and AAT only one case showed staining for AAT and factor XIIIa. As far as MC is concerned, there was expression of both Leu-M, and Lex in a cytoplasmic distribution in all the seven cases. The membranous accentuation of Lex seen in all cases of CC was not present in the cases of MC. Four of the 7 cases of MC showed reactivity for B72-3 as well and the staining pattern of Leu-M, and B72-3 was predominantly both cytoplasmic and membranous. In 3 of the 7 cases of MC, there was expression of monoclonal CEA, in 1 case there was expression of AAT and in 2 cases there was expression of factor XIIIa.Histologic differentiation of HC from CC and MC can be greatly aided by immunohistochemical studies. Using a panel of 7 antibodies, cases of HC displayed cytoplasmic reactivity for AAT, AFP and factor XIIIa. Cases of CC showed membranous and cytoplasmic reactivity for Lex but only cytoplasmic reactivity for Leu-M, and B72-3. On the other hand cases of MC showed only cytoplasmic staining but not membranous accentuation for Lex but Leu-M, and B72-3 showed membranous as well as cytoplasmic staining. The antibody MCEA showed variable results and hence was considered not useful. Therefore the results strongly suggest that a panel of 6 monoclonal antibodies (except MCEA) will greatly help in differentiating between primary and metastatic carcinoma.

SUBMITTER: Mishra R

PROVIDER: S-EPMC5529908 | biostudies-other | 1995 Apr

REPOSITORIES: biostudies-other

ACCESS DATA

Similar Datasets

Project description:AimTo identify the differential proteins associated with colorectal cancer genesis and hepatic metastasis.MethodsHydrophobic protein samples were extracted from normal colorectal mucosa, primary cancer lesion and hepatic metastatic foci of colorectal cancer. With two-dimensional electrophoresis and image analysis, differentially expressed protein spots were detected, and the proteins were identified by matrix assisted laser desorption/ionization-time of flight-mass spectrometry and peptide mass fingerprint analysis.ResultsSignificant alterations of the proteins in number and expression levels were discovered in primary cancer and hepatic metastatic foci, the expression of a number of proteins was lost in 25-40 ku, but protein spots was increased in 14-21 ku, compared with normal mucosa. Nine differentially expressed protein spots were identified. Three proteins expressed in normal mucosa, but lost in primary cancer and hepatic metastasis, were recognized as calmodulin, ribonuclease 6 precursor and mannosidase-alpha. Proapolipoprotein was expressed progressively from normal mucosa to primary cancer and hepatic metastasis. The differentially expressed protein of beta-globin was found in normal mucosa and hepatic metastatic tumor, but lost in primary cancer lesion. Cdc 42, a GTP-binding protein, was identified in hepatic metastasis. The protein spots of C4 from primary cancer, M7 and M9 from hepatic metastasis had less homology with the proteins in database.ConclusionVariations of hydrophobic protein expression in colorectal cancer initiation and hepatic metastasis are significant and can be observed with two-dimensional electrophoresis. The expression of calmodulin, ribonuclease 6 precursor and mannosidase-alpha is lost but the expression of proapolipoprotein is enhanced which is associated with colorectal cancer genesis and hepatic metastasis. Cdc 42 and beta-globin are expressed abnormally in hepatic metastasis. Protein C4, M7 and M9 may be associated with colorectal cancer genesis and hepatic metastasis.

Project description:BackgroundFumarate hydratase-deficient renal cell carcinoma (FH-RCC) is a rare highly aggressive subtype of kidney cancer for which the distinct genomic, transcriptomic, and evolutionary relationships between metastatic and primary lesions are still unclear.MethodsIn this study, whole-exome, RNA-seq, and DNA methylation sequencing were performed on primary-metastatic paired specimens from 19 FH-RCC cases, including 23 primary and 35 matched metastatic lesions. Phylogenetic and clonal evolutionary analyses were used to investigate the evolutionary characteristics of FH-RCC. Transcriptomic analyses, immunohistochemistry, and multiple immunofluorescence experiments were performed to identify the tumor microenvironmental features of metastatic lesions.ResultsPaired primary and metastatic lesions generally showed similar characteristics of tumor mutation burden, tumor neoantigen burden, microsatellite instability score, CNV burden, and genome instability index. Notably, we identified an FH-mutated founding MRCA (the most recent common ancestor) clone that dominated the early evolutionary trajectories in FH-RCC. Although both primary and metastatic lesions manifested high immunogenicity, metastatic lesions exhibited higher enrichment of T effector cells and immune-related chemokines, together with upregulation of PD-L1, TIGIT, and BTLA. In addition, we found that concurrent NF2 mutation may be associated with bone metastasis and upregulation of cell cycle signature in metastatic lesions. Furthermore, although in FH-RCC metastatic lesions in general shared similar CpG island methylator phenotype with primary lesions, we found metastatic lesions displaying hypomethylated chemokine and immune checkpoints related genomic loci.ConclusionsOverall, our study demonstrated the genomic, epigenomic, and transcriptomic features of metastatic lesions in FH-RCC and revealed their early evolutionary trajectory. These results provided multi-omics evidence portraying the progression of FH-RCC.

Dataset Information

CAN IMMUNOHISTOCHEMISTRY DISTINGUISH BETWEEN PRIMARY AND METASTATIC HEPATIC CARCINOMA?

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets