Marker For Small Cell Carcinoma Research Articles

435. A DIAGNOSTIC PITFALL; SMALL CELL CARCINOMA-LIKE FEATURES IN BASALOID SQUAMOUS CELL CARCINOMA OF THE ESOPHAGUS

Abstract Esophageal basaloid squamous cell carcinoma may resemble small cell carcinoma biopsy specimens and cause difficulties in pathology diagnosis. We aimed to explore the pathological features of basaloid squamous cell carcinomas in biopsy specimens that mimic small cell carcinoma and to clarify their diagnostic and prognostic features. This study will contribute to draw attention to an important pitfall in pathology diagnosis in endoscopic biopsy specimens of the esophagus. Thirty biopsy specimens of esophageal basaloid squamous cell carcinoma were reviewed and compared with 13 matched surgical specimens. A small cell carcinoma-like feature was defined as, when at least one of the three following findings was observed: 1) diffuse growth pattern, 2) nuclear molding and 3) nuclear crush artifact. Immunohistochemistry of synaptophysin, chromogranin A, CD56 (neuroendocrine markers) and p16 were performed in all cases. Small cell carcinoma-like features, such as diffuse growth, nuclear molding, or nuclear crush artifact, were identified in 80% (24/30) of the biopsies and in 77% (10/13) of the surgery specimens, but in a proportionally much smaller area in the surgical specimens than in the biopsy samples. The presence of a small cell carcinoma-like feature had no impact on patients´ outcome. Immunohistochemically, synaptophysin and chromogranin A were consistently negative, while CD56 was expressed in 42% (10/24) basaloid squamous cell carcinomas with small cell carcinoma-like features. p16, a highly sensitive marker for small cell carcinoma, was also expressed in 8% (2/24). In conclusion, small cell carcinoma-like features are frequent and conspicuous in biopsies, which may probably be caused by exogenous factors such as friction and external pressure that occur in biopsy procedure and in the tumor environment. Small cell carcinoma-like features may lead to a misinterpretation of a true small cell carcinoma, if CD56 is an only neuroendocrine marker expressed. p16 expression may be also detected in basaloid squamous cell carcinoma.

A diagnostic pitfall; Small cell carcinoma-like features in basaloid squamous cell carcinoma of the esophagus.

Esophageal basaloid squamous cell carcinoma may resemble small cell carcinoma biopsy specimens and cause difficulties in pathology diagnosis. We aimed to clarify the clinicopathological significance of small cell carcinoma-like morphologies in basaloid squamous cell carcinoma. Thirty biopsy specimens of esophageal basaloid squamous cell carcinoma were reviewed and compared with 13 matched surgical specimens. Small cell carcinoma-like features, such as diffuse growth, nuclear molding, or nuclear crush artifact, were identified in 80% (24/30) of the biopsies and in 77% (10/13) of the surgery specimens, but in a proportionally much smaller area in the surgical specimens than in the biopsy samples. The presence of a small cell carcinoma-like feature had no impact on patients´ outcome. Immunohistochemically, synaptophysin and chromogranin A were consistently negative, while CD56 was expressed in 42% (10/24) of basaloid squamous cell carcinomas with small cell carcinoma-like features. p16, a highly sensitive marker for small cell carcinoma, was also expressed in 8% (2/24). p40 was expressed in all cases of basaloid squamous cell carcinoma. In conclusion, small cell carcinoma-like features are frequent and conspicuous in biopsies, which are probably caused by exogenous factors such as friction and external pressure that occur in biopsy procedure and in the tumor environment. Small cell carcinoma-like features may lead to a misinterpretation of a true small cell carcinoma, if CD56 is the only neuroendocrine marker expressed. p16 expression may also be detected in basaloid squamous cell carcinoma.

EVALUATION OF NAPSIN A EXPRESSION IN LUNG CANCERS AND ITS COMPARISON WITH THYROID TRANSCRIPTION FACTOR 1

Introduction: Lung cancer is the leading cause of cancer mortality in the world. With the development of new, successful treatments for adenocarcinoma, it is essential to subtype Non- Small Cell Lung Carcinoma whenever possible. Thyroid Transcription Factor-1 is a promising marker for lung adenocarcinoma but its sensitivity and specificity is limited. Napsin A is a new marker that may be useful as a part of immunohistochemistry panel to classify poorly differentiated lung carcinoma on small biopsies. Aim: To study the expression of Napsin A in lung cancer and to compare it with TTF-1 that has already recognized as a useful marker for lung adenocarcinoma. Methodology: This is a retrospective study. By analyzing the histopathology records during the period of 2015 - 2017, histopathological slides of biopsy proven 50 malignant lung cases were collected. Napsin A expression was tested and compared with TTF1. Results: Adenocarcinoma is the commonest type. Most common age group is 51-60 years with male female ratio is 2.7:1. Smokers have increased risk for malignancy. Napsin A and TTF1 showed similar sensitivity and the specificity of Napsin A was higher than TTF1 to lung adenocarcinoma. Napsin A showed higher sensitivity than TTF1 to exclude lung small cell carcinoma. Conclusion: Napsin A is almost limited to adenocarcinoma, whereas TTF-1 is not so specific. Although TTF-1 is expressed in majority of adenocarcinomas, its expression is also noted in most of the small-cell lung carcinomas. Hence Napsin A can be used as an exclusionary marker for small cell carcinoma. Key words: Lung cancer, Napsin A, Small biopsy, Thyroid transcription factor 1.

Electrochemical immunosensor based on hollow porous Pt skin AgPt alloy/NGR as a dual signal amplification strategy for sensitive detection of Neuron-specific enolase

Neuron-specific enolase (NSE) is a specific marker for small cell carcinoma (SCLC). Sandwich-type electrochemical immunosensors are powerful for biomarker analysis, and the electrocatalytic activity of the signal amplification platform and the performance of the substrate are critical to their sensitivity. In this work, N atom-doped graphene functionalized with hollow porous Pt-skin Ag–Pt alloy (HP–Ag/Pt/NGR) was designed as a dual signal amplifier. The hollow porous Pt skin structure improves the atomic utilization and the larger internal cavity spacing significantly increases the number of electroactive centers, thus exhibiting more extraordinary electrocatalytic activity and durability for H2O2 reduction. Using NGR with good catalytic activity as the support material of HP-Ag/Pt, the double amplification of the current signal is realized. For the substrate, polypyrrole-poly(3,4-ethylenedioxythiophene) (PPy-PEDOT) nanotubes were synthesized by a novel chemical polymerization route, which effectively increased the interfacial electron transfer rate. By coupling Au nanoparticles (Au NPs) with PPy-PEDOT, the immune activity of biomolecules is maintained and the conductivity is further enhanced. Under optimal conditions, the linear range was 50 fg mL−1 - 100 ng mL−1, and the limit of detection (LOD) was 18.5 fg mL−1. The results confirm that the developed immunosensor has great promise for the early clinical diagnosis of SCLC.

Influence of preanalytical variables on performance of delta-like protein 3 (DLL3) predictive immunohistochemistry

DLL3 might become a predictive immunohistochemical marker in small cell carcinoma of the lung (SCLC). We investigated the influence of pre-analytical handling of samples on the performance of DLL3 immunohistochemistry (IHC) using DLL3 SP347 ready to use assay (Ventana). DLL3 positive cell lines were subjected to different experimental conditions mimicking the pre-analytical variation in daily clinical practice. Formalin fixation of 24 h led to the most optimal results of DLL3 IHC. Longstanding fixation in Cytolyt, methanol-based fixative for cytology samples, but also decalcification using a mix of formic- and hydrochloracid resulted in decreased DLL3 staining. Postponed staining of blanc slides for 3 months also decreased DLL3 IHC. Postponed fixation of the SCLC cell lines did not influence the performance of DLL3 IHC, although this might be different in the tissues than in the cell lines. In conclusion, different pre-analytical variables decrease the performance of DLL3 IHC. These findings are essential for implementing novel predictive immunohistochemical biomarkers in daily pathology practice.

INSM1 expression in a subset of thoracic malignancies and small round cell tumors: rare potential pitfalls for small cell carcinoma.

INSM1 is a diagnostic marker for neuroendocrine tumors originating in multiple anatomic sites. In the lung, INSM1 shows 76-97% sensitivity for neuroendocrine tumors overall. Our aim was to characterize INSM1 as a diagnostic marker for small cell carcinoma in the context of its epithelial, lymphoid, and mesenchymal morphologic mimics. Immunohistochemistry was performed on 231 tumors, including lung neuroendocrine tumors, nonneuroendocrine carcinomas of the thoracic cavity, diffuse large B-cell lymphomas, and small round cell sarcomas, using an anti-INSM1 mouse monoclonal antibody. Extent (0-100%) and intensity (1-3+) of nuclear INSM1 staining was multiplied in each case to calculate an H-score. Demographic and clinical information was obtained from the medical record. INSM1 had an overall sensitivity and specificity of 81.5% and 82.7% for small cell carcinoma, respectively, using a threshold established with a receiver operating characteristic curve. 40/48 (82.7%) small cell carcinomas were positive for INSM1, including 19/24 (79%) small cell carcinomas that were negative for chromogranin and synaptophysin. 5/5 carcinoids and 21/28 (75%) large cell neuroendocrine carcinomas showed INSM1 expression. Among nonneuroendocrine tumors, 7/38 (18%) lung adenocarcinomas, 2/17 (12%) lung squamous cell carcinomas, 4/10 (40%) thymic carcinomas, 4/12 (33%) adenoid cystic carcinomas, 1/19 (5%) diffuse large B-cell lymphomas, 4/11 (36%) alveolar rhabdomyosarcomas, and 4/23 (17%) Ewing sarcomas were positive for INSM1. No synovial sarcomas or desmoplastic small round cell tumors were positive. Weak, focal INSM1 expression alone is insufficient as a diagnostic marker for small cell carcinoma, but is sensitive and specific, easy to interpret in small biopsies, and makes a valuable addition to a diagnostic panel.

Insulinoma-associated protein 1 is a novel sensitive and specific marker for small cell carcinoma of the prostate

The correct diagnosis of small cell carcinoma (SCC) of the prostate is critical because of its aggressive behavior and poor prognosis. The histopathologic diagnosis could be challenging without neuroendocrine markers, which currently has limitations. Insulinoma-associated protein 1 (INSM1), a zinc-finger transcription factor, is considered to play an important role in the development of several neuroendocrine precursor cells. Its diagnosis value has only recently been evaluated. In this study, we analyzed the expression of INSM in three high-throughput RNA sequencing data sets and performed INSM1 immunohistochemistry on a large series of prostatic SCCs and non-neuroendocrine prostate tissues. To validate its possible utility as a diagnostic marker, the performance of chromogranin and synaptophysin was used for comparison. We found INSM1 mRNA is up-regulated in neuroendocrine prostate carcinoma samples from the published data sets. The results were verified by the immunohistochemistry performance. INSM1 was positive in 92.3% of prostatic SCCs, compared with 53.8% positive for chromogranin, and 84.6% positive for synaptophysin. INSM1 was also stained all of the mixed SCC-acinar adenocarcinomas and metastatic SCCs progression from acinar adenocarcinoma. Only 3.4% of benign prostate tissues and 4.0% of prostate adenocarcinomas were INSM1 positive. Our data suggest that INSM1 is a novel sensitive and specific marker for detection of SCC of the prostate. Application of INSM1 in clinical pathologic diagnosis will be valuable.

Evaluation of “neuron-specific enolase” as a tumor marker for small cell carcinoma of the lung

Evaluation of “neuron-specific enolase” as a tumor marker for small cell carcinoma of the lung

Immunohistochemical findings in resected lung cancer

The relationship between histological type and immunohistological findings was studied in total 141 cases of resected lung cancer. Adenocarcinoma was cytologically subtyped according to the ultrastructural findings. Immunohistochemical staining was performed on paraffin-embedding tissue using the avidin-biotin-peroxidase complex method for carcinoembryonic antigen (CEA), keratin, secretory component (SC), neuron specific enolase (NSE), lysozyme (Ly) and lactoferrin (La). Adenocarcinoma stained strongly positive with antibody against CEA and SC. There was no statistical difference among the different subtypes of adenocarcinoma, but in the cases of clara cell type, CEA staining was less intense and in goblet cell type, the intensity of SC staining was great. Goblet cell type characteristically stained positively with anti-Ly antibody, and Ly was a specific marker for differentiating adenocarcinoma of goblet cell type. La was positive not only in bronchial gland cell type, but also in other subtypes in adenocarcinoma. Squamous cell carcinoma showed more intense staining with anti-keratin antibody than other histological types. Small cell carcinoma extensively stained with anti-NSE antibody, but some of the other histological types also stained positively. NSE was a relatively good marker for small cell carcinoma but was not specific. It is concluded that immunohistochemical examination is a useful method for differentiation of different histological types of lung cancer.

Perception of breathlessness during bronchoconstriction induced by antigen, exercise, and histamine challenges.

Perception of breathlessness was studied in eight patients with mild, stable asthma after a histamine and exercise challenge performed before and 24 and 48 hours respectively after an antigen challenge. FEV1 and perception of breathlessness, evaluated by Borg's 10 point category scale, were measured after each administration of doubling antigen or histamine concentrations to achieve a greater than 20% fall in FEV1, and after six minutes of steady state exercise at 80% of maximal oxygen consumption (VO2max). The geometric mean provocative concentration of histamine causing a 20% fall in FEV1 (PC20) fell from 1.67 mg/ml before antigen challenge to 0.52 mg/ml 24 hours after the challenge. The median maximal % fall in FEV1 with exercise was 24.9% (range 10.5-40.5%) before and 30.6% (range 13.8-52.3%) 48 hours after antigen challenge. The median maximum % fall in FEV1 after antigen inhalation was 20.1% (range 13.3-35.2%) within the first hour; only two subjects had a late fall in FEV1 (23% and 58%). The median (range) of Borg scores obtained when FEV1 was reduced by 20% did not differ significantly for the three types of acute challenges: 1.25 (0.5-2.5) and 1.0 (0.5-3.0) after histamine tests, 1.0 (0.5-4.1) and 1.55 (0.5-2.0) after exercise, and 1.5 (0-3.0) after antigen challenge. In the two subjects who had a late response to antigen the Borg score was reduced for the same % fall in FEV1 as with the early response. It is concluded that the perception of breathlessness does not differ appreciably during the early response to histamine, antigen exposure, or exercise, but that it is reduced during the late asthmatic response. It was not influenced by previous antigen exposure, despite an increase in airway responsiveness.

Presence of high concentration of 7B2 in pleural effusion.

7B2 (a novel pituitary protein) is a secretory protein in the neuroendocrine tissues and an increase in the plasma 7B2 concentration was noted in some patients with various endocrine tumors, including small cell carcinoma of the lung and acromegaly, suggesting that 7B2 is a possible marker for these tumors. Using a radioimmunoassay, the 7B2 concentration was measured in pleural fluid samples obtained from 36 patients with lung cancer and benign pulmonary disease to assess its concentration as a marker for small cell carcinoma of the lung (SCCL) or malignant effusion. 7B2-immunoreactivity (IR) was present in pleural fluid and its concentration was much higher than in plasma. However, there was no significant difference between pleural fluid 7B2 in patients with SCCL and in other histological types of lung carcinoma or in malignant and nonmalignant patients. In the chromatographic analysis of pleural fluid on gel permeation chromatography and reverse-phase high-performance liquid chromatography, there was no molecular heterogeneity between malignant and nonmalignant effusion. These results suggest that pleural fluid 7B2-IR is not a useful marker for SCCL or malignant effusion.

Increased plasma motilin concentrations in small cell carcinoma of the lung.

Plasma samples from 21 patients with small cell carcinoma of the lung were screened for pancreatic polypeptide, somatostatin, motilin, and vasoactive intestinal polypeptide. One patient had severe impairment of both renal and liver function. In the 20 remaining subjects vasoactive intestinal polypeptide concentrations were normal, and only two patients had increased concentrations of somatostatin. Increases in pancreatic polypeptide were detected more commonly (7/20), but these may have been non-specific age related increases. The major finding was high concentrations of motilin (greater than 496 pg/ml) in 17 of 20 patients. Plasma motilin was subsequently assayed in 16 more patients with lung cancer, including 10 patients with non-small cell carcinoma of the lung. At concentrations over 900 pg/ml plasma motilin appears to be a tumour marker for small cell carcinoma of the lung with acceptable sensitivity (59%) and specificity (78%). The origin of increased plasma motilin in small cell carcinoma of the lung was investigated. Bombesin (gastrin releasing peptide), a peptide known to stimulate the release of motilin in man, was, as in previous studies, detected in tumour but not in plasma, except in one patient out of 21. Immunohistochemical studies failed to detect motilin antigen in biopsy samples. Motilin tumour content was found to be low in tumour tissue from three patients with small cell carcinoma of the lung who had appreciable hypermotilinaemia and from three patients with non-small cell carcinoma of the lung who had either normal or slightly raised plasma motilin concentrations. The stimulus to motilin secretion in patients with small cell carcinoma of the lung remains unclear.

Neurone specific enolase: A useful diagnostic serum marker for small cell carcinoma of the lung

Neurone specific enolase: A useful diagnostic serum marker for small cell carcinoma of the lung

Neurone specific enolase: a useful diagnostic serum marker for small cell carcinoma of the lung.

Among lung cancers small cell carcinoma is the most sensitive to chemotherapy and radiation. This has emphasised the importance of an accurate diagnosis of this cell type, and the present study examined the use of serum neurone specific enolase (NSE) as a diagnostic marker for small cell carcinoma. NSE was measured in pretreatment sera from 103 patients with small cell carcinoma and in sera from relevant controls, including patients with other lung cancers, non-malignant lung diseases, and healthy adults. Serum NSE concentration was raised (greater than 25 ng/ml) in 72% of patients with small cell carcinoma. Ninety one per cent of patients with extensive disease and 50% of patients with limited disease were serum NSE positive. Patients with extensive disease in general had higher serum NSE concentrations than patients with limited disease. No definite difference in serum NSE positivity could be shown between oat cell and intermediate cell subtypes. Out of 51 patients with other lung cancers, four (8%) had a raised serum concentration, whereas all patients with non-malignant diseases and healthy individuals had normal serum NSE concentrations. Serum NSE determination seems to be a valuable tool for the diagnosis of small cell carcinoma.