Localization of type III procollagen aminopeptide antigenicity in hepatocytes from cirrhotic human liver

Summary Immunolocalization of type III procollagen (pro III) in normal and cirrhotic human liver was studied using rabbit antiserum specific for bovine type III procollagen aminopeptide. The material examined was deparaffinized, trypsin-treated hepatic tissue sections from 28 autopsy cases, including 19 cirrhotic and 9 normal liver donors. Immunostaining, performed by the unlabeled peroxidase-antiperoxidase antibody technique demonstrated that extracellular matrices corresponding to perisinusoidal reticulin, collagen in periportal areas, and blood vessel walls were the common sites of pro III antigenicity in both normal and cirrhotic liver. Moreover, in the cirrhotic liver, the fibrous septa of pseudolobules, and cytoplasm of hepatocytes and sinusoidal cells were positive when stained for pro III peptide. The differential counts of pro III positive cells in cirrhotic liver, however, revealed that the average ratio of these hepatocytes to sinusoidal cells was 25 to 1, indicating complete dominance of hepatocytes with respect to stainability for pro III peptide compared to sinusoidal cells. In hepatocellular carcinomas co-existing with cirrhosis, neoplastic cells also displayed pro III antigenicity.These data suggest that hepatocytes of cirrhotic liver and hepatocellular carcinoma cells play a significant role in type III collagen synthesis in vivo.The paper on this problem was read at the International Symposium on Pathobiology of Hepatic Fibrosis held in Matsue, Japan, on June 16, 1985     

NPC2 expression in thyroid tumors and its possible diagnostic utility

Histopathologic diagnosis of thyroid lesions is sometimes difficult and may require the assistance of immunohistochemistry. Currently-used immunohistochemical biomarkers share the weakness of staining both papillary thyroid carcinoma and other non-papillary thyroid lesions. We examined NPC2 as an immunohistochemical marker in various thyroid lesions to determine the subcellular localization of the immunohistochemistry signal and evaluated the value of NPC2 as a diagnostic marker of papillary thyroid carcinoma. NPC2 immunostaining was performed on various thyroid tumors and tumor-like lesions. The immunostaining revealed significantly different patterns for papillary carcinomas and the other lesions. Papillary carcinomas exhibited moderate to strong granular cytoplasmic staining, often with basal membranous accentuation. In contrast, the other lesions showed mostly weak cytoplasmic staining, often with apical membranous accentuation. The subcellular localization of NPC2 provided insight into contrasting histopathologic morphology and reversed cellular polarity between the papillary patterns of papillary carcinomas and the follicular patterns of non-papillary carcinoma lesions. The diagnostic characteristics of NPC2 immunohistochemistry for non-follicular papillary carcinomas versus non-papillary carcinoma lesions were a sensitivity of 97.3%, specificity of 96.9%, positive predictive value of 94.7%, and negative predictive value of 98.4%. Significant differences were present between the two staining patterns in papillary carcinoma relative to mean age, nodal metastasis, and follicular and non-follicular variants (P = 0.02, P = 0.03, and P = 0.000, respectively). In conclusion, our evaluation of the subcellular localization of NPC2 using immunohistochemistry demonstrated possible value of NPC2 as a biomarker and provided insight into the morphologic characteristics of papillary carcinoma.     

Loss of intracellular peroxidase and anaplastic change of differentiated carcinoma of human thyroid gland

Ultrastructural localization of endogenous peroxidase (peroxidase) in differentiated thyroid carcinoma was studied in 2 cases of follicular carcinoma and 12 of papillary carcinoma. The reaction product for the enzyme was observed in cancer cells which had a round and smoothly-contoured nucleus and rather few number of microvilli (positive cells) and the product localized mainly in the rough-surfaced endoplasmic reticulum and perinuclear cisternae. The positive cells resembled normal follicular cells in localization sites of the reaction product and ultrastructural features. On the contrary, in cancer cells having an irregularly-outlined nucleus with or without intranuclear cytoplasmic inclusion and many microvilli, no reaction product was visualized (negative cells). The positive cells were frequently found in 2 follicular carcinomas and 2 papillary carcinomas. Only a few number of positive cells presented in 2 papillary carcinomas. The remaining 8 papillary carcinomas were composed only of negative cells. Histologically, follicles with colloid were frequently found in carcinomas with abundant positive cells, whereas they were few in number in carcinomas containing only negative cells. These findings suggest that loss of peroxidase activity in cancer cells of follicular cell origin correlates with anaplastic change of the cancer cells.     

Immunolocalization of type III collagen and procollagen in cirrhotic human liver using monoclonal antibodies

Summary Immunolocalization of type III collagen and procollagen in cirrhotic human liver was studied using monoclonal antibody specific for the helical determinant of type III collagen extracted from human placenta. Deparaffinized, trypsin-treated cirrhotic liver sections from 8 autopsy cases were examined by the unlabeled peroxidase-antiperoxidase and immunofluorescence techniques. These techniques revealed the localization of this epitope shared by type III collagen and procollagen not only in the extracellular matrix of hepatocytes and sinusoidal cells but also in the cytoplasm. In hepatocellular carcinoma concurrent with cirrhosis, neoplastic cells were shown to react with this antibody as well.These results are consistent with data obtained using antiserum specific for bovine type III procollagen aminopeptide which appeared in our previous report.     

Immunohistochemical localization of metal binding proteins in thyroid tissues and tumors

Positive immunohistochemical staining for three metal binding proteins, ceruloplasmin, lactoferrin, and transferrin, has been suggested to be a reliable diagnostic marker of malignant but not benign thyroid neoplasms. We tested this hypothesis on a series of 9 nodular hyperplasias, 17 follicular adenomas, 54 papillary carcinomas, 20 follicular carcinomas, and 3 anaplastic carcinomas of thyroid using formalin-fixed paraffin-embedded tissues. We found focal staining for ceruloplasmin and lactoferrin in approximately 25% of follicular adenomas examined; focal ceruloplasmin positivity was also seen in nonneoplastic tissues surrounding thyroid neoplasms. No staining for these markers was found in malignant neoplasms or hyperplasias. Transferrin was found in 55% of papillary carcinomas, but more follicular adenomas (20%) than follicular carcinomas (11%) were positive using this antiserum. These findings show that immunostaining for these antigens is not a reliable method to distinguish benign from malignant thyroid lesions of follicular cell origin.     

LOSS OF INTRACELLULAR PEROXIDASE and ANAPLASTIC CHANGE OF DIFFERENTIATED CARCINOMA OF HUMAN THYROID GLAND

Ultrastructural localization of endogenous peroxidase (peroxidase) in differentiated thyroid carcinoma was studied in 2 cases of follicular carcinoma and 12 of papillary carcinoma. The reaction product for the enzyme was observed in cancer cells which had a round and smoothly-contoured nucleus and rather few number of microvilli (positive cells) and the product localized mainly in the rough-surfaced endoplasmic reticulum and perinuclear cisternae. The positive cells resembled normal follicular cells in localization sites of the reaction product and ultrastructural features. On the contrary, in cancer cells having an irregularly-outlined nucleus with or without intranuclear cytoplasmic inclusion and many microvilli, no reaction product was visualized (negative cells). The positive cells were frequently found in 2 follicular carcinomas and 2 papillary carcinomas. Only a few number of positive cells presented in 2 papillary carcinomas. The remaining 8 papillary carcinomas were composed only of negative cells. Histologically, follicles with colloid were frequently found in carcinomas with abundant positive cells, whereas they were few in number in carcinomas containing only negative cells.
These findings suggest that loss of peroxidase activity in cancer cells of follicular cell origin correlates with anaplastic change of the cancer cells.     

Differential nuclear and cytoplasmic expression of PTEN in normal thyroid tissue, and benign and malignant epithelial thyroid tumors

Germline mutations in PTEN (MMAC1/TEP1) are found in patients with Cowden syndrome, a familial cancer syndrome which is characterized by a high risk of breast and thyroid neoplasia. Although somatic intragenic PTEN mutations have rarely been found in benign and malignant sporadic thyroid tumors, loss of heterozygosity (LOH) has been reported in up to one fourth of follicular thyroid adenomas (FAs) and carcinomas. In this study, we examined PTEN expression in 139 sporadic nonmedullary thyroid tumors (55 FA, 27 follicular thyroid carcinomas, 35 papillary thyroid carcinomas, and 22 undifferentiated thyroid carcinomas) using immunohistochemistry and correlated this to the results of LOH studies. Normal follicular thyroid cells showed a strong to moderate nuclear or nuclear membrane signal although the cytoplasmic staining was less strong. In FAs the neoplastic nuclei had less intense PTEN staining, although the cytoplasmic PTEN-staining intensity did not differ significantly from that observed in normal follicular cells. In thyroid carcinomas as a group, nuclear PTEN immunostaining was mostly weak in comparison with normal thyroid follicular cells and FAs. The cytoplasmic staining was more intense than the nuclear staining in 35 to 49% of carcinomas, depending on the histological type. Among 81 informative tumors assessed for LOH, there seemed to be an associative trend between decreased nuclear and cytoplasmic staining and 10q23 LOH (P = 0.003, P = 0.008, respectively). These data support a role for PTEN in the pathogenesis of follicular thyroid tumors.     

Expression of D2-40 in adjunct diagnosis of papillary thyroid carcinoma

The clinical pathologic criteria for nuclear features of papillary thyroid carcinoma are subjective and sometimes cannot distinguish carcinoma from adenomatous goiter and follicular neoplasms. No single antibody has demonstrated high sensitivity or specificity in making these distinctions. Using quantitative analysis of immunohistochemical staining with D2-40, a recently available monoclonal antibody used as a lymphatic endothelial marker, we examined 72 cases of papillary carcinoma. Controls included 36 follicular adenomas, 36 follicular carcinomas, and 20 adenomatous goiters with papillary hyperplasia. Cytoplasmic D2-40 immunoreactivity was present in 60 of 72 papillary carcinomas, 2 cases of follicular adenoma and 2 cases of follicular carcinoma, whereas no adenomatous goiter or normal thyroid glands contained positive epithelial cells. Overexpression of D2-40 in papillary thyroid carcinomas thus has potential diagnostic utility in differentiating these tumors from their potential histologic mimics.     

Presence of immunoreactive corticotropin releasing hormone in thyroid lesions.

Corticotropin-releasing hormone (CRH) functions as a regulator of the hypothalamic-pituitary-adrenal axis and coordinator of the stress response. Immunoreactive CRH (IrCRH) is also produced in a variety of inflammatory sites, where this peptide acts as a proinflammatory cytokine. To detect CRH in autoimmune thyroid disease as well as in disorders that may be associated with an inflammatory reaction within this gland, we examined immunohistochemically 45 thyroid lesions, including 12 nodular goiters, 9 cases of Hashimoto thyroiditis, 6 follicular adenomas, 4 follicular and 8 papillary carcinomas, 4 Hürthle cell tumors, 1 medullary cancer, and 1 insular thyroid carcinoma. We also examined the presence of IrCRH in the adjacent normal thyroid parenchyma. The avidin-biotin complex method was employed on formalin-fixed, paraffin-embedded tissue, using a highly specific, affinity-purified polyclonal rabbit anti-CRH antibody. Granular cytoplasmic immunostaining of follicular cells was observed in 100% of the cases of Hashimoto thyroiditis, 77% of the neoplasms and 42% of goiters. The intensity of the staining was more pronounced in Hashimoto thyroiditis and Hürthle cell tumors, whereas the remaining lesions exhibited a heterogeneous staining pattern. No IrCRH was observed in the normal thyroid parenchyma. Using a specific radioimmunoassay, the IrCRH in extracts of simple thyroid goiters, papillary carcinomas, and Hürthle cell tumors ranged between 0.031 and 0.224 pmol/g of wet tissue but was undetectable in normal thyroid parenchyma. The IrCRH molecule in the thyroid gland eluted at the same fraction as synthetic rat/human CRH 1-41 in reverse phase high pressure liquid chromatography. We conclude that IrCRH is present in thyroid lesions, predominantly in those related to autoimmune phenomena, suggesting that this neuropeptide may be directly and/or indirectly involved with inflammatory processes taking place in this gland.     

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.     

Pattern of expression of intermediate cytokeratin filaments in the thyroid gland: an immunohistochemical study of simple and stratified epithelial-type cytokeratins

The expression of simple and stratified epithelial-type cytokeratin (CK) intermediate filaments was evaluated by immunohistochemistry in a series of 41 papillary carcinomas, 10 follicular carcinomas, 2 poorly differentiated carcinomas and 34 specimens of normal thyroid parenchyma and lymphocytic thyroiditis. The aim of the study was to establish the CK profile of normal thyroid and thyroid carcinomas in order to clarify the putative application of CK immunostaining in diagnostic surgical pathology, and to evaluate whether the process of neoplastic transformation and tumour progression in the thyroid may be associated with any particular change in CK expression. Normal thyroid strongly expressed simple epithelial-type CKs 7 and 18 and, to a lesser degree, CKs 8 and 19, but did not express stratified epithelial-type CKs. The same pattern was found in lymphocytic thyroiditis, though the CK 19 immunoreactivity was stronger in these lesions than in the normal thyroid. Papillary and follicular thyroid carcinomas shared the expression of simple epithelial-type CKs 7, 8, 18 and 19. Immunoreactivity for CK 19 was frequently stronger and more widely distributed within each particular tumour in papillary than in follicular carcinomas, but it could also be detected, at least focally, in every follicular carcinoma. Strong expression of CK 19 highlighted small foci of papillary carcinoma not easily identifiable by conventional histological examination. Stratified epithelial-type CKs 5/6 and 13 were detected in a high percentage of papillary carcinomas, in contrast to their absence in follicular carcinomas and normal thyroid. The CK pattern was similar in primary and metastatic papillary carcinomas. We conclude that papillary carcinoma of the thyroid presents a distinct CK profile that may be used for diagnostic purposes.     

CD98 expression is decreased in papillary carcinoma of the thyroid and Hashimoto’s thyroiditis

Aims: CD98 is a component of the large neutral amino acid transporter (LAT), which is a cell surface amino acid transporter. CD98 also binds to and activates β₁‐integrin, promoting anchorage‐independent growth. CD98 expression is increased in a variety of carcinomas but its distribution in the normal and neoplastic thyroid gland has not been reported. The aim was to examine the immunohistochemical expression of CD98 in normal and diseased thyroid tissue. Methods and results: One hundred and forty thyroid cases were selected from the archives of the Department of Pathology, including normal controls, neoplasms (follicular adenoma, follicular carcinoma and papillary carcinoma) and non‐neoplastic conditions (multinodular goitre, Graves’ disease and Hashimoto’s thyroiditis). Immunohistochemistry for CD98 was performed and each case was scored for proportion of cells and intensity of immunoreactivity. In normal thyroid, there was moderately strong expression of CD98 in the lateral cell membranes of follicular cells. A similar pattern of expression was seen in follicular adenoma, minimally invasive follicular carcinoma, multinodular goitre and Graves’ disease. In most cases of papillary carcinoma and in the inflamed areas of Hashimoto’s thyroiditis, expression of CD98 was decreased. Conclusions: CD98 expression is down‐regulated in thyroid papillary carcinoma; this may relate to the better prognosis associated with many of these tumours.     

Differential expression of S100C in thyroid lesions

Identification of new potential markers that may help in the diagnosis of benign and malignant thyroid lesions is needed. By comparative 2-dimensional gel electrophoresis of microdissected cells from tumors and normal thyroid tissue, we identified a new protein, S100C, which is highly expressed in papillary carcinomas. In order to validate this finding, we investigated the immunohistochemical expression and the potential role in diagnosis of these markers in 94 specimens representing the spectrum of malignant and benign thyroid lesions. Normal thyroid tissue was evaluated in 57 specimens. Galectin-3, a marker reported as specific for malignant lesions, was also evaluated in the same lesions. S100C protein was expressed in the nuclei of normal tissue, hyperplastic nodules, and follicular adenomas and carcinomas. Papillary carcinomas showed a strong, but cytoplasmic, pattern of staining. Galectin-3 immunostaining was strongly positive in papillary carcinomas, and negative in benign lesions, confirming its value in differential diagnosis. These findings suggest that immunohistochemical staining of S100C could be helpful in the pathological study of thyroid lesions, especially in cases in which follicular variants of papillary carcinoma and follicular carcinoma are considered in the differential diagnosis.     

Patterns of basement membrane laminin distribution in nonneoplastic and neoplastic thyroid tissue.

Laminin, a major basement membrane component, is typically absent or partially lost around the epithelial elements of most invasive carcinomas. To evaluate the distribution of laminin in both primary and metastatic thyroid tumors, we studied 14 benign thyroid lesions (eight adenomas, two Graves' disease, two Hashimoto's thyroiditis, one adenomatous hyperplasia, one nodular goiter), 20 carcinomas (seven papillary, six tall cell variant, four follicular, three Hürthle), and eight metastases (five tall cell variant, three follicular) utilizing a polyclonal antibody against highly purified, nidogen-free laminin. All benign lesions showed positive, linear immunostaining along basement membranes. Partial loss or absence of laminin was seen in the solid areas of all types of thyroid carcinomas examined; well-differentiated papillary and follicular tumors, as well as papillary and follicular areas of more poorly differentiated neoplasms, maintained linear laminin immunostaining in the papillary cores beneath the epithelial cells and around follicles. A similar correlation between laminin deposition and architectural organization was seen in metastatic lesions. Hürthle cell carcinomas had a unique fragmented, pericellular immunostaining pattern around individual tumor cells, suggesting uncontrolled laminin synthesis. Our findings suggest that preservation of laminin production in thyroid tumors reflects their degree of differentiation and that absence of laminin correlates with lack of structural organization rather than reflecting invasive and metastatic potential.     

High-level expression, activation, and subcellular localization of p38-MAP kinase in thyroid neoplasms

The p38 family of MAP kinases (p38-MAPKs) is involved in regulating the proliferation, survival, and migration of various cancer cells. The present study has investigated the expression, subcellular localization, phosphorylation, and activity of p38-MAPKs in normal and tumoural human thyroid tissues and in thyroid cell lines. The expression and nucleo-cytosolic compartmentalization of the alpha-isoform of p38-MAPKs (p38alpha-MAPK) were studied by western blotting in the WRO and B-CPAP cell lines, which are derived from human follicular and papillary thyroid carcinomas, respectively, and in the non-transformed rat thyroid cell lines FRTL-5 and PCCL3. Immunohistochemistry was used to study the expression and subcellular localization of p38alpha-MAPK, and of the phosphorylated forms of p38-MAPKs (P-p38-MAPKs) in human toxic adenomas (TAs), follicular adenomas (FAs), papillary thyroid carcinomas (PTCs), and follicular thyroid carcinomas (FTCs). The activity of p38-MAPKs in PTCs and FTCs was revealed by immunohistochemical detection of their typical phosphorylated substrate, MAPK-activated protein kinase 2/3 (MK2/3). p38alpha-MAPK was expressed in all cell lines and this expression was restricted to the cytosolic compartment. p38 MAPK activity was involved in regulating DNA synthesis in B-CPAP cells. p38alpha-MAPK and P-p38-MAPKs were strongly expressed in PTC and FTC cells, although only in the cytoplasm, whereas they were only very weakly expressed in FA cells, and absent in adjacent normal tissues. They were also expressed at a high level in TAs, but they were found in both nucleus and cytoplasm. Finally, phospho-MK2/3 immunostaining followed very similar patterns to those of p38alpha-MAPK and P-p38-MAPKs in PTCs and FTCs. Taken together, these results show for the first time that the p38-MAPK signalling cascade is functional in two types of differentiated carcinoma of the thyroid. The observation that p38-MAPK hyper-expression occurs in FTC, but not in FA, may provide an additional diagnostic tool for malignancy in some thyroid nodules.     

胃动素及其前体mRNA在正常人甲状腺和甲状腺肿瘤组织中表达的研究

目的 探讨胃动素和胃动素前体mRNA基因在正常人甲状腺的表达,比较人甲状腺胃动素前体mRNA基因序列与人小肠胃动素前体mRNA基因序列的异同;观察胃动素活性肽和胃动素前体mRNA在甲状腺肿瘤中的表达,并比较它们在良、恶性甲状腺肿瘤表达的异同及临床意义.方法 采用RT-PCR、Southern杂交和分子克隆等技术,克隆并测定人甲状腺和人小肠黏膜内胃动素前体mRNA基因序列;采用荧光免疫组织化学双染技术、Western印迹和即时荧光定量PCR(real-time PCR),观察胃动素和胃动素前体mRNA在正常甲状腺和甲状腺良、恶性肿瘤组织中表达的异同.结果 (1)正常人甲状腺组织有胃动素和胃动素前体mRNA的表达,且胃动素和降钙素共表达于同一细胞,即甲状腺C细胞;(2)人甲状腺组织内胃动素前体mRNA基因序列与基因库报道的人小肠胃动素前体mRNA基因序列(BC112314,NCBI,美国)完全相同;(3)免疫荧光组织化学、Western印迹以及real-time PCR结果均显示,正常人甲状腺和甲状腺肿瘤组织内均有胃动素和胃动素前体mRNA的表达,其中甲状腺髓样癌和嗜酸性腺瘤胃动素及其前体mRNA的表达高于正常甲状腺组织(均P＜0.05);但甲状腺乳头状癌和滤泡癌胃动素和胃动素前体mRNA的表达则明显降低(均P＜0.05);而结节性甲状腺肿与正常甲状腺组织相比胃动素和胃动素前体mRNA的表达差异均无统计学意义(P＞0.05).结论 人甲状腺组织有胃动素和胃动素前体mRNA的表达,且胃动素主要表达于甲状腺C细胞;人甲状腺组织胃动素前体mRNA基因序列与人小肠胃动素前体mRNA基因序列完全相同;甲状腺髓样癌和嗜酸性腺瘤内胃动素及其前体mRNA的表达明显增高,而甲状腺乳头状癌和滤泡癌内胃动素及其前体mRNA的表达明显降低.提示胃动素可能通过影响甲状腺滤泡旁细胞的分泌活动参与其生理活动的调节,胃动素可能与临床甲状腺髓样癌和甲状腺嗜酸性腺瘤疾病的发生和发展有关.     

Reduced HBME-1 immunoreactivity of papillary thyroid carcinoma and papillary thyroid carcinoma-related neoplastic lesions with Hürthle cell and/or apocrine-like changes

BACKGROUND: We have recently observed that Hürthle cell tumours and papillary thyroid carcinoma with tumour cells showing decapitation of luminal portion of the cytoplasm (apocrine-like changes) display negative or decreased immunoreactivity for HBME. The purpose of this study is to correlate papillary thyroid carcinoma with positive and negative immunoreactivity for HBME with the histopathological features. METHODS AND RESULTS: Two hundred and five thyroid neoplasms including carcinoma and adenomas were grouped into Hürthle cell tumours, tumours with or without some features of Hürthle cells, tumours with apocrine-like changes and adenomas with or without limited nuclear features of papillary thyroid carcinoma but not diagnostic for papillary thyroid carcinoma. All neoplasms were submitted for immunostaining with cytokeratin 19 (CK19) and HBME. Papillary thyroid carcinoma, follicular carcinoma and follicular adenoma that have areas of limited nuclear features but not diagnostic for papillary thyroid carcinoma showed stronger immunostaining for HBME than their respective counterparts with Hürthle cell changes. All Hürthle cell tumours showed negative to focal reactivity. This decrease of reactivity for HBME was proportional to the levels of Hürthle cell changes. In addition, focal to extensive apocrine-like changes were seen in most Hürthle cell neoplasms and rarely seen in non-Hürthle cell neoplasms. Apocrine-like changes abolished or decreased HBME immunoreactivity of papillary thyroid carcinoma and tumours with limited nuclear features. Immunostaining for cytokeratin AE3 was not affected by Hürthle cell or apocrine-like changes. CONCLUSIONS: All papillary thyroid carcinomas without Hürthle cell or apocrine-like differentiation are reactive for HBME. Hürthle cell tumours and tumours with Hürthle cell or apocrine-like changes show negative or focal reactivity for HBME. Except for this limitation, HBME is a sensitive marker for papillary thyroid carcinoma and tumours with limited nuclear features.     

Immune characterization of thyroid neoplasm's and its variants using immunohistochemical markers: CK-19, Galectin-3 and Hector Battifora mesothelial-1

BackgroundNodular lesions of the thyroid are amongst the common palpable lesions that are encountered by the pathologists in the fine needle aspiration clinics and not only aspiration smears, but even biopsy sections pose significant challenges in their characterization and further classification. Neoplastic lesions of the thyroid have shown a steady rise worldwide and are diagnosed at age younger than most other cancers. Histopathology remains the gold standard in diagnosis and classification of thyroid neoplasms, with variable sensitivity and specificity of immunohistochemical markers, also attributed to variation in the inclusion criteria. We classified the thyroid neoplasms based on WHO Classification (2017) and aimed to study the diagnostic utility of immunohistochemical markers - CK-19, Galectin-3 and Hector Battifora mesothelial-1 performed on manual tissue microarray sections to differentiate various variants of papillary carcinoma from its mimickers, specifically follicular patterned papillary neoplasms from other follicular patterned lesions.MethodProspective study of neoplastic lesions of thyroid from July 2018 to August 2020. Authors describe the clinico-radiological, cytological, histo-morphological and immunohistochemical features of neoplastic nodular lesions of the thyroid.ResultsProspective analysis of nodular thyroid lesions yielded 76 cases, of which 38 were neoplastic. Cytology showed discordance in 10/24 cases, amongst the discordant cases, 70% were confirmed as papillary carcinoma. CK-19 showed high expression in all variants of papillary carcinomas (24/24), low expression in well differentiated tumor of uncertain malignant potential (WD-TUMP) and medullary carcinoma. It was negative in follicular and Hurthle cell neoplasms. Galectin-3 showed 100% specificity and HBME-1 showed 100% sensitivity in diagnosis of papillary carcinoma and its variants. Adenomatoid nodules did not express Gal-3 which helped in their differentiation from FVPTC.ConclusionsGal-3 in combination either with CK-19 or HBME-1 improves the sensitivity and specificity of detection of papillary carcinoma, its variants and its differentiation from follicular patterned lesions to 100% with a significant p value.     

A novel stem cell associated marker identified by monoclonal antibody HESC5:3 differentiates between neoplastic lesions in follicular thyroid neoplasms

Follicular thyroid lesions are the bane of cytopathology. Differentiation between adenoma and carcinoma is impossible, and often these neoplasms are indistinguishable even from uninodular goitre. In other cancers as well, a theory of stem cells as the origin of cancer has been discussed in thyroid carcinogenesis. We aimed to examine a novel stem cell associated marker identified by monoclonal antibody HESC5:3 in follicular lesions in an attempt to find a marker for differential diagnosis in thyroid cytopathology. HESC5:3 was raised against and is specific for undifferentiated human embryonic stem cells. The epitope of this novel antibody is to be defined. Immunohistochemical expression of HESC5:3 was examined in clinical material comprised of follicular neoplasms (83 adenomas, 43 carcinomas) and non‐neoplastic lesions (41 goitrous, 22 hyperplastic, 23 normal tissue specimens). Staining differed significantly between neoplastic and non‐neoplastic lesions. Nuclear staining was increased in non‐neoplastic cells, whereas in neoplastic cells expression was mainly cytoplasmic. There was no difference between benign and malignant lesions, suggesting a role in early tumourigenesis. In conclusion, the HESC5:3 epitope may be of benefit as a neoplasia marker in distinguishing between uninodular goitre and neoplasia. Characterization of the epitope would increase the interest in this promising new stem cell associated marker.