[Diagnostic problems in parathyroid disease].
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Humans↗
Biomedical subjects
M Papotti
Publications and source records attributed to M Papotti.
Expression of somatostatin receptor types 1-5 in 81 cases of gastrointestinal and pancreatic endocrine tumors. A correlative immunohistochemical and reverse-transcriptase polymerase chain reaction analysis.
Somatostatin receptors (SSTRs) have been extensively mapped in human tumors by means of autoradiography, reverse-transcriptase polymerase chain reaction (RT-PCR), in situ hybridization (ISH) and immunohistochemistry (IHC). We analyzed the SSTR type 1-5 expression by means of RT-PCR and/or IHC in a series of 81 functioning and non-functioning gastroenteropancreatic (GEP) endocrine tumors and related normal tissues. Moreover, we compared the results with clinical, pathological and hormonal features. Forty-six cases (13 intestinal and 33 pancreatic) were studied for SSTR 1-5 expression using RT-PCR, IHC with antibodies to SSTR types 2, 3, 5 and ISH for SSTR2 mRNA. The vast majority of tumors expressed SSTR types 1, 2, 3 and 5, while SSTR4 was detected in a small minority. Due to the good correlation between RT-PCR and IHC data on SSTR types 2, 3, and 5, thirty-five additional GEP endocrine tumors were studied with IHC alone. Pancreatic insulinomas had an heterogeneous SSTR expression, while 100% of somatostatinomas expressed SSTR5 and 100% gastrinomas and glucagonomas expressed SSTR2. Pre-operative biopsy material showed an overlapping immunoreactivity with that of surgical specimens, suggesting that the SSTR status can be detected in the diagnostic work-up. It is concluded that SSTRs 1-5 are heterogeneously expressed in GEP endocrine tumors and that IHC is a reliable tool to detect SSTR types 2, 3 and 5 in surgical and biopsy specimens.
Adult↗
Cortistatin-14 inhibits cell proliferation of human thyroid carcinoma cell lines of both follicular and parafollicular origin.
Cortistatin (CST-14, Pro-c[Cys-Lys-Asn-Phe-Phe-Trp-Lys-Thr-Phe-Ser-Ser-Cys]-Lys-NH2), a neuropeptide member of the SRIH family, binds to all 5 SRIH receptor (sst) subtypes, but also possesses a significant binding affinity to GH secretagogue receptors (GHS-R), which have been reported to mediate the antiproliferative activity of GHS on thyroid cancer cells. The effect of CST-14 on cell proliferation was studied in 3 different human thyroid carcinoma cell lines of follicular origin (N-PAP, WRO, ARO) and in one thyroid medullary carcinoma cell line (TT). CST-14 1 pM determined a significant inhibition of cell proliferation in TT, N-PAP and WRO cells and this effect was dose-dependent and more pronounced than that displayed by SRIH-14 (Ala-Gly-c[Cys-Lys-Asn-Phe-Phe-Trp-Lys-Thr-Phe-Thr-Ser-Cys]-OH) treatment. To a minor extent, CST-14, but not SRIH-14, also temporary inhibited ARO cell proliferation. By immunofluorescence, sst2, sst3 and sst5 have been demonstrated in TT cells, whereas types 3 and 5 only were expressed in N-PAP and WRO cells, and no sst subtype was found in ARO cells. The presence of both GHS-Rla and lb mRNA has been studied and demonstrated in the TT medullary carcinoma cell line, whereas follicular derived cell lines were already known to express GHS binding sites. Addition of EP-80874 (D-Mrp-c[D-Cyspyridilalanyl3-D-Trp-Lys-Val-Cys]-Mrp-NH2), a synthetic peptide that binds to SRIH and GHS-R, completely abolished the antiproliferative effects of CST-14 or SRIH-14 on sst/GHS-R positive thyroid carcinoma cell lines (WRO, N-PAP and TT). EP-80874 was also able to antagonize the inhibitory activity of CST-14 on the growth of cells (ARO) expressing GHS-R but not sst. Taken together, these data firstly demonstrate that EP-80874 has a mixed SRIH/CST antagonist activity and suggest that the oncostatic effect of CST-14 on thyroid cancer cells could be mediated by both sst and/or GHS-R.
Adenocarcinoma, Follicular↗
Specific haplotypes of the RET proto-oncogene are over-represented in patients with sporadic papillary thyroid carcinoma.
BACKGROUND: Papillary thyroid carcinoma (PTC), which may be sporadic (95%) or familial (5%), has a prevalence adjusted for age in the general population of 1:100 000. Somatic rearrangements of the RET proto-oncogene are present in up to 66% of sporadic tumours, while they are rarely found in familial cases. PURPOSE: In order to determine if some variants of this gene, or a combination of them, might predispose to PTC, we looked for an association of RET haplotype(s) in PTC cases and in controls from four countries matched for sex, age, and population. METHODS: Four single nucleotide polymorphisms (SNPs) across the RET coding sequence were typed and haplotype frequencies were estimated. Genotype and haplotype distributions were compared among these cases and controls. RESULTS: Ten haplotypes were observed, the seven most frequent of which have been previously described in sporadic Hirschsprung patients and controls. The single locus analyses suggested association of exon 2 and exon 13 SNPs with sporadic PTC. The haplotype analysis showed over-representation of one haplotype in French and Italian sporadic PTC, whereas a different haplotype was significantly under-represented in French familial PTC. CONCLUSIONS: Our data suggest that some variants of RET and some specific haplotypes may act as low penetrance alleles in the predisposition to PTC.
Age Factors↗
Localization of a susceptibility gene for familial nonmedullary thyroid carcinoma to chromosome 2q21.
The familial form of nonmedullary thyroid carcinoma (NMTC) is a complex genetic disorder characterized by multifocal neoplasia and a higher degree of aggressiveness than its sporadic counterpart. In a large Tasmanian pedigree (Tas1) with recurrence of papillary thyroid carcinoma (PTC), the most common form of NMTC, an extensive genomewide scan revealed a common haplotype on chromosome 2q21 in seven of the eight patients with PTC. To verify the significance of the 2q21 locus, we performed linkage analysis in an independent sample set of 80 pedigrees, yielding a multipoint heterogeneity LOD score (HLOD) of 3.07 (alpha=0.42), nonparametric linkage (NPL) 3.19, (P=.001) at marker D2S2271. Stratification based on the presence of at least one case of the follicular variant of PTC, the phenotype observed in the Tas1 family, identified 17 such pedigrees, yielding a maximal HLOD score of 4.17 (alpha=0.80) and NPL=4.99 (P=.00002) at markers AFMa272zg9 and D2S2271, respectively. These results indicate the existence of a susceptibility locus for familial NMTC on chromosome 2q21.
Carcinoma, Papillary↗
Application of an immunodiagnostic method for improving preoperative diagnosis of nodular thyroid lesions.
BACKGROUND: Thyroid cancer is the most common endocrine malignant disease, but preoperative diagnosis remains a challenge. Fine-needle aspiration cytology has greatly improved the clinical management of thyroid nodules, but the preoperative characterisation of follicular lesions is very difficult. Many patients are thus referred to surgery more for diagnosis than for therapeutic necessity. We undertook an international multicentre study to assess the usefulness of immunohistocytochemical staining for two potential markers of malignant thyrocytes. METHODS: Expression of galectin-3 and CD44v6 was tested on 1009 thyroid lesions (tissue specimens and cytological cell-blocks) and 226 fresh cytological samples obtained preoperatively by ultrasound-guided fine-needle aspiration of thyroid nodules (prospective analysis). The test used monoclonal antibodies specific for CD44v6 and galectin-3, the indirect avidin-biotin complex immunoperoxidase method, and 3-amino-9-ethyl-carbazole as substrate. FINDINGS: The sensitivity, specificity, positive predictive value, and diagnostic accuracy of this test method (for coexpression of the two markers) in the prospective analysis were 88%, 98%, 91%, and 97%, respectively. The sensitivity and specificity of galectin-3 immunodetection alone in discriminating benign from malignant thyroid lesions were more than 99% and 98% respectively, and the positive predictive value and diagnostic accuracy were 92% and 99%. INTERPRETATION: The integration of galectin-3 immunostaining with conventional cytomorphological and clinical diagnostic procedures represents a sensitive and reliable diagnostic approach for preoperative identification of thyroid carcinomas. This test method improves the diagnostic accuracy of conventional cytology and provides the molecular basis for a new nosological assignation of the not yet classified thyroid neoplasms of indeterminate malignant behaviour.
Antigens, Differentiation↗
Immunohistochemical localization of adenosine A1 receptors in human brain regions.
Adenosine exerts its physiological actions by binding to G-protein coupled receptors, four of which have been identified and cloned to date (A1, A2a, A2b and A3). Here we report the development of anti-human adenosine A1, receptor anti-peptide polyclonal antibodies and their use to define the distribution of A1, receptors in human brain regions, spinal cord and trigeminal ganglia by an immunohistochemical approach. Although the distribution of adenosine A1, receptor and its mRNA in the human brain has been investigated in the past by autoradiography and in situ hybridization, this is the first demonstration of localization of the A1, receptors by immunohistochemical means. Our localization data broadly agree with immunohistochemical data published for the human brain obtained using other experimental approaches. Furthermore, we have demonstrated the novel finding that abundant expression of the adenosine A1, receptor protein occurs in the trigeminal ganglia, which may be suggestive of a role of this receptor in analgesia.
Adult↗
Cortistatin, but not somatostatin, binds to growth hormone secretagogue (GHS) receptors of human pituitary gland.
Antagonism between GH secretagogues (GHS) and somatostatin (SRIH) has been postulated and demonstrated, but SRIH does not bind to GHS receptors (GHS-R) and potent synthetic peptidyl GHS (GHRP6, hexarelin) do not displace radiolabeled SRIH from its receptors. However, non-natural SRIH octapeptide agonists (mainly lanreotide and vapreotide) displace 125I-Tyr-Ala-hexarelin from pituitary binding sites suggesting that an endogenous factor related to SRIH might exist and interact with GHS-R. Our aims were to investigate the ability of different SRIH-like peptides such as various SRIH fragments (SRIH 3-14, SRIH 7-14, SRIH 3-10, SRIH 7-10, SRIH 2-9) and a natural neuropeptide that shows a high structural homology with SRIH such as cortistatin-14 (CST) to compete with 125I-Tyr-Ala-hexarelin for human pituitary binding sites and to compare their binding affinity with that of hexarelin and ghrelin, a gastric-derived peptidyl GHS that has been proposed as a natural ligand of GHS-R. While the binding of 125I-Tyr-Ala-hexarelin to pituitary membranes was completely displaced by unlabelled hexarelin, ghrelin and CST, none of the SRIH fragments tested inhibited this binding. Ghrelin and CST exhibited a similar affinity (4.6-5.4 x 10(-7) mol/l) for the binding while hexarelin was more effective by about four orders of magnitude in displacing 125I-Tyr-Ala-hexarelin. Our data demonstrate for the first time that cortistatin, a natural peptide related to SRIH, binds to GHS-R and suggest that this factor may play a role in modulating the activity of these receptors.
Adult↗
Binding of 125I-labeled ghrelin to membranes from human hypothalamus and pituitary gland.
Ghrelin has been proposed as a natural ligand of the GH secretagogue receptor(s) (GHS-R), which was an orphan receptor activated by synthetic peptidyl (hexarelin) and non-peptidyl (MK-0677) GHS to strongly release GH in animals and humans. Herein we studied: 1) the binding of 125I-labeled human ghrelin to membranes from human hypothalamus and pituitary gland; 2) the ability of human ghrelin (either octanoylated or desoctanoylated), as well as of some GHS and neuropeptides to compete with the radioligand. The saturation binding analysis showed, in both tissues, the existence of a single class of high-affinity binding sites with limited binding capacity. The Bmax (maximal number of binding sites) values of ghrelin receptors in the hypothalamus were significantly greater (p<0.001) than those detected in the pituitary, whereas the Kd (dissociation constant) values in the two tissues were similar. 125I-ghrelin bound to hypothalamic membranes was displaced by ghrelin, hexarelin, MK-0677, various GHS antagonists (EP-80317, [D-Arg1-D-Phe5-D-Trp7,9-Leu11]-substance P) and some natural (cortistatin-14) and synthetic (vapreotide) SRIH-14 agonists. In contrast, no competition was seen in the presence of GHRH-44, SRIH-14 or desoctanoylated ghrelin, a ghrelin precursor that is devoid of GH-releasing properties. In conclusion, this preliminary study firstly demonstrates that ghrelin needs octanoylation to bind its hypothalamo-pituitary receptors. These receptors are the specific binding sites for GHS and their antagonists, as well as for SRIH analogs (vapreotide and cortistatin- 14), but not for native SRIH.
Binding, Competitive↗
Genetic alterations in poorly differentiated endocrine colon carcinomas developing in tubulo-villous adenomas: a report of two cases.
The genetic study of two cases of tubulovillous adenoma associated with poorly differentiated endocrine carcinoma (PDEC) is reported. Aim of this work was to assess whether the exocrine and endocrine growths share a common genotype. The analysis entailed the search for allelic loss (LOH) or imbalances of polymorphic microsatellite markers at the corresponding chromosomal loci of the genes MEN-1 (11q13), p53 (17p13). Deleted in Colorectal Carcinoma (DCC) (18q21) and hMSH-2 (BAT26) (2p21-22). Additionally, the exons 5-8 of the p53 gene were sequenced in the two PDECs only. One of the two cases investigated showed LOH for 18q DCC markers in the tubulo-villous adenoma while a point mutation of the p53 gene was observed in the PDEC component. No genetic abnormality was observed in both adenoma and PDEC components of the other case. In the two cases p53 protein accumulation was observed in both PDEC and adenoma cells. These data indicate that only the p53 gene abnormality is shared by both colon cancer and PDEC in the two cases reported. The lack of other common genetic defect may suggest a different histogenesis for the two tumor types. The development of colon PDEC implies the defect of p53 gene.
Adenoma, Villous↗
Expression of somatostatin receptor types 2, 3 and 5 in biopsies and surgical specimens of human lung tumours. Correlation with preoperative octreotide scintigraphy.
The increasingly popular use of somatostatin analogs in clinical practice for both diagnostic and therapeutic purposes prompted extensive investigations on somatostatin receptor (sst) expression in human tumors by autoradiography, nucleic acid analysis and, recently, immunohistochemistry (IHC). The currently employed radiotracer for scintigraphy (Octreoscan) is octreotide, a somatostatin analog having a high affinity for sst types 2, 3, and 5. In this study on 25 patients, we compared sst 2, 3, and 5 expression in surgical and biopsy specimens of lung tumors, as revealed by immunohistochemical and reverse transcriptase polymerase chain reaction (RT-PCR), with the octreoscan outcome (which was positive in 20/25 cases). By IHC, the tumors mainly expressed sst2 (17/25, 68%) at the cell membrane level, while sst 3 and 5 were detected in a fraction of cases (24% and 20%, respectively). Comparing RT-PCR and IHC data, a correlation was found in 83.3% of cases, while octreoscan findings and sst expression were correlated in 22/25 cases (88%). In addition, cytological and biopsy specimens expressed the same sst type found in the corresponding surgical sample, thus indicating that a cell membrane sst immunoreactivity in a biopsy reliably predicts the tumor-receptor profile before its resection. Finally, sst expression was not restricted to neuroendocrine lung tumors, but was also a feature of some non-neuroendocrine carcinomas, although to a lesser extent. The occasional expression of sst subtypes in intratumoral lymphocytes, endothelia and necrotic areas is an additional feature to be considered in the interpretation of Octreoscan findings, since the in vivo procedure does not allow to define the sst cellular distribution. IHC can therefore be usefully coupled to radionuclear investigations to better characterize the sst cellular location and subtype in lung tumors.
Adenocarcinoma↗
Frequent RET rearrangements in thyroid papillary microcarcinoma detected by interphase fluorescence in situ hybridization.
Papillary thyroid microcarcinomas (measuring 1 cm or less in diameter) are very common thyroid tumors, which are present in 10% to 35% of post-mortem histopathological examinations of individuals whose death was due to a cause other than thyroid cancer. The molecular basis of this tumor is still poorly understood. Somatic mutations are better characterized in clinically evident papillary thyroid carcinomas (PTCs), the most common involving the proto-oncogene RET, which maps to 10q11.2. Molecular alterations of RET always lead to intra- or interchromosomal rearrangements. In this study we have investigated the status of RET in 21 microcarcinomas, by means of interphase fluorescence in situ hybridization (FISH). RET was rearranged in 52% of microcarcinomas, a statistically significant higher frequency than that found previously in clinically evident PTCs using the same technique. Moreover, interphase FISH allowed us to detect a putative novel type of rearrangement in a microcarcinoma, and we observed trisomies of chromosome 10 and other chromosomes in two adenomas surrounding two of the microcarcinomas. The strikingly high frequency of RET rearrangements in microcarcinomas strongly suggests that RET plays a role in the initiation of thyroid tumorigenesis but does not seem to be necessary for the further progression of the tumor.
Adult↗
Expression of apocrine differentiation markers in neuroendocrine breast carcinomas of aged women.
Neuroendocrine (NE) breast carcinomas are a rare entity in young women; however, their frequency increases in aged patients. The present work demonstrates that NE breast carcinomas in elderly women can also express an apocrine immunophenotype and analyzes the histological and clinical aspects of such differentiation. A selected series of 50 NE tumors (positive for NE markers in >/=50% of the cells) was tested for the immunocytochemical expression of gross cystic disease fluid protein-15 (GCDFP-15). The results demonstrated that about 50% of moderately (G2) and well-differentiated (G1) NE breast carcinomas (mucinous, solid papillary, and solid cohesive histotypes) coexpressed the apocrine marker. In these cases, specific mRNA for GCDFP-15 (PIP) and for chromogranin A (ChA) was demonstrated using in situ hybridization (ISH). Carcinomas of the alveolar subtype (G2) and poorly differentiated carcinomas (G3), including one case of atypical carcinoid, were pure NE carcinomas, devoid of apocrine differentiation. The steroid receptor status of these lesions was evaluated to test a possible involvement of androgen receptors in apocrine differentiation. We demonstrated that the level of AR and the mean age of patients at diagnosis were significantly higher in apocrine than in nonapocrine differentiated tumors. The histological grade and the expression of estrogen receptor (ER) significantly influenced the prognosis of these NE carcinomas, either pure or NE-apocrine differentiated. The most original result of our study is therefore the demonstration of a possible divergent apocrine differentiation of NE breast carcinomas that might be regulated by the activation of androgen receptors in elder patients. In addition, the possibility for using Chs or GCDFP-15 serum values in the follow-up of these patients, as demonstrated in two cases of the present series, can justify the immunophenotyping of the tumors.
Adenocarcinoma, Mucinous↗
Immunohistochemical detection of somatostatin receptor types 1-5 in medullary carcinoma of the thyroid.
BACKGROUND: We have analysed the distribution of the five somatostatin receptors (sst1-5) by immunohistochemistry in a large retrospective series of 51 medullary carcinoma of the thyroid (MCT) specimens and correlated the pattern of sst expression with expression of somatostatin (SRIF) peptide, tumour pathology and clinical outcome. MEASUREMENTS: Immunohistochemistry was performed with rabbit polyclonal antipeptide antibodies directed against the extracellular domains or cytoplasmic tail of human (h) sst1-5. SRIF immunoreactivity was investigated in parallel paraffin sections. RESULTS: Eighty-five percent of the tumours were positive for one or more sst, localized to both tumour cells as well as surrounding peritumoural structures, especially blood vessels. Forty-nine percent of the tumours were positive for sst1, 43% for sst2, 47% for sst3, 4% for sst4, and 57% for sst5. Fifty-one percent of tumours expressed one or two sst subtypes; 33% were positive for three or more sst isoforms. All five sst receptors were detected in only two cases. Tumours expressing octreotide sensitive subtypes (sst2,3,5) accounted for 75% of the series. 50% of the tumours co-expressed SRIF suggesting tumour cell regulation by endogenous SRIF via paracrine/autocrine circuits. There was no correlation between sst1-5 expression and age, sex, tumour size or stage, histological type or clinical outcome. Simultaneous analysis of primary tumour and lymph node metastases revealed a similar pattern of sst immunoreactivity indicating that sst expression is not modified in the course of disease progression. CONCLUSIONS: With the exception of sst4, medullary carcinoma of the thyroid display a rich but heterogeneous expression of sst subtypes. Immunohistochemical typing of sst receptor expression using specific antireceptor antibodies represents an ideal approach for characterizing sst subtype expression in medullary carcinoma of the thyroid for optimizing receptor targeted diagnosis and therapy with somatostatin analogs.
Adult↗
Thyroid transcription factor 1 and cytokeratins 1, 5, 10, 14 (34betaE12) expression in basaloid and large-cell neuroendocrine carcinomas of the lung.
Basaloid carcinoma (BC) and large-cell neuroendocrine carcinoma (LCNEC) are 2 recently recognized variants of large-cell lung carcinomas that may overlap in their morphology, and are discriminated by expression of neuroendocrine markers in LCNEC. Because thyroid transcription factor 1 (TTF-1) is expressed in lung adenocarcinomas but not in squamous cell carcinomas (SCC), and 34betaE12 recognizes a set of high-molecular-weight cytokeratins characteristic of basal stem cells, we hypothesized that these 2 markers could help in distinguishing BC from LCNEC. Immunostaining for TTF-1 was detected in 40.9% of pure LCNEC but in no BC or basaloid variant of SCC. In contrast, immunoreactivity for 34betaE12 was shown in all BC and basaloid variant of SCC but in only 1 LCNEC. Bouin fixation was less efficient than formalin in the immunodetection of both markers for its well-known deleterious effect on antigen preservation. Specificity of TTF-1 for LCNEC (100%) and that of 34betaE12 for BC (98.3%) exceeded that of NE markers for distinction of these 2 entities. These data show that TTF-1 and 34betaE12, in association with specific neuroendocrine markers, represent a useful panel of antibodies in differentiating carcinomas presenting with a solid pattern, palisading, or pseudorosettes, the expression of TTF-1 excluding the diagnosis of BC, and staining with 34betaE12 excluding pure LCNEC.
Carcinoma, Large Cell↗
Clinical significance of neuroendocrine carcinoma of the breast.
BACKGROUND: Neuroendocrine (NE) carcinomas of the breast are defined by the diffuse expression of NE markers. This definition includes lesions with 'pure' NE phenotype as well as 'variants' which may co-express mucinous and/or apocrine phenotype. In the present work, the clinical significance of pure' NE differentiation in breast carcinoma and of its 'variants' will be analyzed. MATERIALS AND METHODS: Forty-three NE breast carcinomas immunocytochemically positive for chromogranins and/or synaptophysin in > or = 50% of cells were graded following the Elston and Ellis grading system for breast carcinomas. The production of mucin and the expressionof the apocrine marker Gross Cystic Disease Fluid Protein-15 (GCDFP-15) were correlated with the grade and the hormonal receptor status. The clinical outcome of patients was also analyzed. RESULTS: The histological grade highly influenced the clinical evolution of NE breast carcinomas. We confirmed that mucinous differentiation is an important indicator of low biological aggressiveness. Estrogen and progesterone receptor expression was also correlated with a better prognosis. Presence of androgen was correlated with the expression of GCDFP-15 in NE tumors. CONCLUSIONS: The histological grade overcomes the immunophenotype in determining the prognosis of NE differentiated carcinomas of the breast. Co-expression of exocrine products in such tumors is related to hormone dependency.
Apolipoproteins↗
Secondary and tertiary hyperparathyroidism: causes of recurrent disease after 446 parathyroidectomies.
OBJECTIVE: To determine, in a series of patients with secondary and tertiary parathyroid hyperplasia, whether the type of parathyroidectomy (subtotal, total with autotransplantation, or total), the histologic pattern of the parathyroid tissue, or the proliferative index, as determined by Ki-67 analysis, could predispose patients to recurrent hyperparathyroidism. SUMMARY BACKGROUND DATA: Recurrent hyperparathyroidism appears in 10--70% of the patients undergoing surgery for secondary or tertiary hyperparathyroidism. The incidence could be related to the type of operation (Rothmund) but also depends on the histologic pattern of the glands removed (Niederle). METHODS: The retrospective investigation was performed on 446 patients undergoing parathyroid surgery. They were also studied in relation to the possibility of renal transplantation. In this population, two homogeneous groups were subsequently identified (23 patients with clear signs of recurrence and 27 patients apparently cured); they were studied from the histologic and immunohistochemical point of view using antibody to Ki-67 antigen. RESULTS: Subtotal parathyroidectomy, total parathyroidectomy with autotransplantation, and total parathyroidectomy produced similar results when considering the regression of osteodystrophy, pruritus, and ectopic calcification. As one could anticipate, total parathyroidectomy increased the incidence of hypoparathyroidism. The percentage of recurrence was 5% to 8% after subtotal parathyroidectomy, total parathyroidectomy with autotransplantation, and total parathyroidectomy, and only after incomplete parathyroidectomy did this percentage climb to 34.7%. In the recurrence group, the nodular form was more common and the proliferative fraction detected by Ki-67 was 1.9%; it was 0.81% in the control group. CONCLUSIONS: Because more radical procedures were not more effective, the authors favor a less radical procedure such as subtotal parathyroidectomy. Histologic patterns and proliferative fraction could be useful indices of a recurrence, and these patients should be watched closely after surgery.
Adult↗
34betaE12 cytokeratin immunodetection in the differential diagnosis of neuroendocrine carcinomas of the breast.
Neuroendocrine (NE) carcinomas of the breast share morphologic and immunohistochemical features with NE tumors of other sites, either resembling typical carcinoids or the highly aggressive small cell carcinoma. In addition, some mucinous carcinomas or solid/papillary carcinomas may show a major NE component. This is generally recognized by specific immunodetection of pan-endocrine markers, although this approach may fail to recognize NE tumors lacking immunoreactivity for some NE products, because the antigen is produced but not retained in the cytoplasm. It has recently been reported that high molecular weight (HMW) cytokeratin (CK), recognized by clone 34betaE12, immunostaining selectively labels non-NE carcinomas (squamous-cell and adenocarcinomas) of the aerodigestive tract and lung. The role of such CK immunodetection in the differential diagnosis of NE carcinoma of the breast was evaluated. Twenty-four cases of breast carcinomas having NE differentiation were selected. Twenty-four cases of non-NE invasive breast carcinomas served as controls. HMW CK immunoreactivity was found in all but one case of non-NE carcinomas, but in only two NE tumors (having scattered positive cells only). The authors conclude that in breast carcinomas the presence of HMW CK immunoreactivity favors the diagnosis of non-NE carcinoma, whereas its absence supports that of a NE tumor (either a carcinoid or a small cell carcinoma or a mucinous carcinoma). HMW CK can be added to the list of markers useful in the differential diagnosis of NE from non-NE tumors.
Biomarkers, Tumor↗