The risk of developing a second primary cancer is increased in patients with breast cancer, and the lung is one of the major sites involved. Moreover, the lung is the major metastatic site for breast ...cancers. A distinction between metastatic breast cancer and primary lung cancer can be histologically difficult, and both show an overlapping CK7+/CK20- immunoprofile in a majority of cases. The degree of difficulty increases with poorly differentiated tumors. We investigated differential expressions of TTF-1, Napsin A, surfactant apoprotein A, estrogen receptor, GATA-3, mammaglobin, and GCDFP-15 immunostains in 197 pulmonary carcinomas (158 adenocarcinomas, 39 squamous) and 115 invasive mammary carcinomas (91 ductal, 24 lobular type). In mammary carcinomas, estrogen receptor, GATA-3, mammaglobin, and GCDFP-15 were expressed in 74, 72, 64, and 62%, respectively, whereas TTF-1, Napsin A, and surfactant apoprotein A were all negative. The expressions were diffuse in estrogen receptor and GATA-3, and variable in mammaglobin and GCDFP-15. For a combination of estrogen receptor/mammaglobin or GATA-3/mammaglobin, 83% of mammary carcinomas were positive, and the detection rate was not improved by using all three markers. All lung squamous cell carcinomas were negative for all markers studied. TTF-1, Napsin A, and surfactant apoprotein A were positive in 80, 77, and 45% of pulmonary adenocarcinomas. None of the TTF-1-negative tumors expressed surfactant apoprotein A. GCDFP-15 was focally expressed in 2.5% of pulmonary adenocarcinomas, and estrogen receptor was focally expressed in one case (1.2%) of pulmonary adenocarcinoma. When metastasis from breast cancer is suspected in the lung, a combination of either estrogen receptor/mammaglobin or GATA-3/mammaglobin as breast markers, and a combination of TTF-1 and Napsin A as lung markers may be helpful for differentiating between the two. Caution should be taken in the interpretation of GCDFP-15 due to its occasional expression in pulmonary adenocarcinomas.
Testicular germ cell tumors (GCTs) are subclassified to seminoma and nonseminomatous GCT for the purpose of treatment and prognostication. This study examined SOX2 and SOX17 expression patterns in a ...total of 67 cases, including 41 pure GCTs (32 seminomas and 9 embryonal carcinomas) and 26 mixed GCTs (9 foci of seminoma, 21 of embryonal carcinoma, 17 of yolk sac tumor, 19 of teratoma, and 5 of choriocarcinoma). All seminoma components showed diffuse SOX17 nuclear expression and were negative for SOX2. All but one of the embryonal carcinomas showed diffuse SOX2 nuclear expression with the one showing a focal reaction, whereas all were negative for SOX17. SOX17 was variably expressed in all yolk sac tumor components, but SOX2 was negative. Teratomas showed variable SOX2 and SOX17 expressions in the epithelial elements. Choriocarcinomas were negative for SOX2 and SOX17. SOX2 and SOX17 expression patterns can distinguish between seminoma and embryonal carcinoma, and this distinction may be diagnostically useful.
Glial cells missing 2 (Gcm2) is a master regulatory gene of parathyroid gland development, and it is exclusively expressed in the parathyroid gland. Diagnostic application of anti-Gcm2 antibody has ...not been reported yet. In this study, a total of 58 cases of parathyroid lesions including 40 adenomas, 2 atypical adenomas, 2 carcinomas, 9 hyperplastic lesions, 4 parathyroid cysts, and 1 case of recurrent hyperplasia of an autograft gland were stained with anti-Gcm2 antibody. Anti-Gcm2 was also applied to a variety of endocrine tumors, including thyroid tumors and nonendocrine tumors, and normal tissues from a variety of organs, including the parathyroid and thyroid glands. Gcm2 nuclear expression was seen in all the normal parathyroid glands, and cystic, hyperplastic, and neoplastic parathyroid lesions in a diffuse manner, whereas no Gcm2 expression was seen in any other normal tissues and tumors, including those of the thymus and thyroid gland. Anti-Gcm2 antibody is a highly sensitive and specific marker for parathyroid lesions. Although the immunohistochemistry stain for parathyroid hormone is a useful marker, its reaction tends to be variable in extent and intensity in parathyroid neoplasia, and it is often negative in parathyroid cysts, and Gcm2 would serve as a useful adjunct marker.
To provide better quality healthcare services to patients with different linguistic and cultural backgrounds, the cross-cultural competence of medical professionals is important. However, assessing ...and improving the cross-cultural competence of healthcare professionals is difficult in Japan, as there is no standardized scale to measure the competence. This study's purpose was to translate the Cross-Cultural Competence instrument for Healthcare Professionals (CCCHP), which was developed and used in Europe, and to examine its reliability and validity among Japanese nurses.
During June and July 2021, nursing staff were invited to take web- and paper-based surveys in Okinawa Japan. The CCCHP (five-factor model with 27 items across motivation, attitude, skills, emotion, and knowledge) was translated using a combination translation method, and a five-point Likert scale was used for responses. Exploratory and confirmatory factor analyses and known-group method were used to examine structural validity, while Cronbach's alpha coefficient was used to test reliability.
A total of 294 responses were analyzed; 77.2% had more than five years of experience. Since the fit index indicated that the five-factor model was not a good fit, it was modified to a four-factor model (J-CCCHP24) by moving three variables, removing the knowledge factor, and using the error covariance of the variables. The fit index after the modification was improved to comparative fit index (CFI) = 0.92, Tucker-Lewis index (TLI) = 0.91, root mean square error of approximation (RMSEA) = 0.05, and standardized root mean square residual (SRMR) = 0.06, and Cronbach's alpha was 0.85. The mean scores of J-CCCHP24 were significantly higher in the group with a history of overseas travel, higher foreign language skill, training in intercultural care, experience of foreign patient care, and intercultural interactions outside the workplace than in the group without these characteristics.
This study confirmed the validity and reliability of the modified Japanese version of the CCCHP (four-factor model with 24 items). The results suggest that the exposure to different cultures on a personal level may help improve nurses' cross-cultural competence. Further refinement of this scale for practical use would encourage the implementation of necessary countermeasures to improve the cross-cultural competence of Japanese healthcare professionals.
Sox10: a pan-schwannian and melanocytic marker Nonaka, Daisuke; Chiriboga, Luis; Rubin, Brian P
The American journal of surgical pathology,
09/2008, Letnik:
32, Številka:
9
Journal Article
Recenzirano
S100 protein is a sensitive marker for melanomas and peripheral nerve sheath tumors. It is, however, expressed by other mesenchymal and epithelial tumors. Despite its low specificity, S100 protein is ...valuable for the diagnosis of desmoplastic melanomas and peripheral nerve sheath tumors, for which no specific marker is available. Sox10 is a neural crest transcription factor crucial for specification, maturation, and maintenance of Schwann cells and melanocytes. Anti-Sox10 antibody was applied to a variety of neural crest-derived tumors, mesenchymal and epithelial neoplasms, and normal tissues. Sox10 nuclear expression was found in 76 of 78 melanomas (97%) and 38 of 77 malignant peripheral nerve sheath tumors (49%) whereas S100 protein was expressed in 71 melanomas (91%) and 23 malignant peripheral nerve sheath tumors (30%). Sox10 was diffusely expressed in schwannomas and neurofibromas. Sox10 reaction was seen only in sustentacular cells of pheochromocytomas/paragangliomas, and occasionally carcinoid tumors from various organs, but it was not seen in the tumor cells. In normal tissues, Sox10 was expressed in Schwann cells, melanocytes, and myoepithelial cells of salivary, bronchial, and mammary glands. Sox10 reaction was not identified in any other mesenchymal and epithelial tumors except for myoepitheliomas and diffuse astrocytomas. Sox10 was expressed by metastatic melanomas and nodal capsular nevus in sentinel lymph nodes, but not by other lymph node components such as dendritic cells. Our results indicate that Sox10 will serve as a more sensitive and specific marker for the diagnosis of melanocytic and schwannian tumors than S100 protein.
Small-cell lung cancer (SCLC), an aggressive neuroendocrine tumor with early dissemination and dismal prognosis, accounts for 15-20% of lung cancer cases and ∼200,000 deaths each year. Most cases are ...inoperable, and biopsies to investigate SCLC biology are rarely obtainable. Circulating tumor cells (CTCs), which are prevalent in SCLC, present a readily accessible 'liquid biopsy'. Here we show that CTCs from patients with either chemosensitive or chemorefractory SCLC are tumorigenic in immune-compromised mice, and the resultant CTC-derived explants (CDXs) mirror the donor patient's response to platinum and etoposide chemotherapy. Genomic analysis of isolated CTCs revealed considerable similarity to the corresponding CDX. Most marked differences were observed between CDXs from patients with different clinical outcomes. These data demonstrate that CTC molecular analysis via serial blood sampling could facilitate delivery of personalized medicine for SCLC. CDXs are readily passaged, and these unique mouse models provide tractable systems for therapy testing and understanding drug resistance mechanisms.
The ovary is a common site of involvement for metastasis and the breast is one of the most common sources. Metastatic breast carcinoma can mimic a primary ovarian carcinoma. Pax8 is a crucial ...transcription factor for organogenesis of the thyroid gland, kidney, and Müllerian system, and it also regulates Wilms tumor suppressor gene (WT1) expression. A total of 124 cases of ovarian carcinomas (84 serous papillary, 18 endometrioid, 12 mucinous, 10 clear cell) and 243 cases of invasive breast carcinomas (178 ductal, 65 lobular) were immunostained with Pax8 and WT1 by tissue microarrays to see the differential expression. Pax8 reaction was found in 108 of 124 ovarian carcinomas (87.1%) generally in diffuse staining, including 81 of 84 serous papillary carcinomas (96.4%), 16 of 18 endometrioid carcinomas (88.9%), 10 of 10 clear cell carcinomas (100%), and 1 of 12 mucinous carcinomas (8.3%), whereas WT1 expression was seen in 78 of 124 ovarian carcinomas (62.9%), including 73 of 84 serous papillary carcinomas (86.9%), and 5 of 18 endometrioid carcinomas (27.8%), with no expression in all 10 clear cell carcinomas and 12 mucinous carcinomas. All the mammary carcinomas were completely negative for Pax8, but WT1 expression was seen in 5 of 243 cases (2.1%). Pax8 is a useful marker in the differential diagnosis of ovarian and breast carcinomas, and it seems to be superior to WT1 for the diagnosis of all types of nonmucinous ovarian carcinomas, notably clear cell and endometrioid types where WT1 expression is generally negative or only focal.
Recently, Orthopedia Homeobox (OTP) was described as a prognostic marker for pulmonary carcinoid tumors; however, little is known about the function and distribution pattern of this transcription ...factor in normal organs/tissues and in tumors. Consequently, OTP expression was investigated in a variety of tumors, with special interest in pulmonary and nonpulmonary neuroendocrine tumors (NETs) and high-grade neuroendocrine carcinomas. OTP immunohistochemical analysis was performed on a total of 162 pulmonary carcinoid tumors, 31 pulmonary neuroendocrine hyperplasias, 104 pulmonary high-grade neuroendocrine carcinomas (large cell neuroendocrine and small cell neuroendocrine), 102 nonpulmonary NETs (G1/G2 NETs, small cell and large cell neuroendocrine carcinomas, and Merkel cell carcinomas), 150 endocrine tumors (thyroid, parathyroid, adrenocortical, and pheochromocytomas/paragangliomas), 279 adenocarcinomas, and 88 squamous cell carcinomas of various organs, including those of the lungs and others. In addition, normal tissues from various organs were studied. OTP nuclear expression was seen in 80% of lung carcinoid tumors. Among other tumors, 4 small-cell carcinomas showed focal expression (2 pulmonary and 2 bladder), but all other tumors were completely negative. Overall, the sensitivity and specificity of OTP were 80.2% and 99.4%, respectively. All TTF1-positive lung carcinoid tumors were diffusely positive for OTP, but none of the OTP-negative carcinoid tumors was positive for TTF1. OTP expression was not seen in any normal tissues/organs. OTP was also negative in neuroendocrine cells of the normal bronchus/bronchiole. However, OTP was strongly expressed in neuroendocrine hyperplasia, including reactive and preneoplastic hyperplasia. Our results suggest that OTP may serve as a useful diagnostic marker for lung carcinoid tumors.
Thyroid-specific transcription factors, Pax8, TTF-1, and TTF-2, are crucial for thyroid organogenesis and differentiation. Compared with TTF-1, the other two markers have scarcely been investigated ...in surgical pathology. The goal of this study is to evaluate the expressions of these markers in thyroid tumors of the full spectrum of differentiation, with special emphasis on anaplastic carcinomas. A total of 94 cases of thyroid neoplasms were studied: 17 papillary carcinomas, 18 follicular adenomas, 16 follicular carcinomas, 7 poorly differentiated carcinomas, 28 anaplastic carcinomas, and 8 medullary carcinomas. Immunostains for these three markers were performed. The antibodies to Pax8 and TTF-2 were also applied on 147 lung carcinomas as well as a variety of normal tissues and malignant tumors. All three markers were seen in papillary carcinomas, follicular adenomas and carcinomas, and poorly differentiated carcinomas in a diffuse manner, whereas their expressions in medullary carcinomas were variable. Pax8 was expressed in 79% of anaplastic carcinomas to a variable extent, whereas TTF-1 and TTF-2 were seen only in 18 and 7% of anaplastic carcinomas, respectively. TTF-2 was negative in all other neoplastic and non-neoplastic tissues including those of the lung. Pax8 was expressed in renal tubules, fallopian tubes, ovarian inclusion cysts, and lymphoid follicles as well as renal carcinoma, nephroblastoma, seminoma, and ovarian carcinoma, but not in normal tissue and carcinomas of the lung. Pax8 is a useful marker for the diagnosis of anaplastic carcinomas, particularly when the differential diagnosis includes pulmonary carcinoma. In differentiated thyroid neoplasms, no significant difference in expression was seen in all the three transcription factors.
The monocarboxylate transporter 1 (MCT1) inhibitor, AZD3965, is undergoing phase I evaluation in the United Kingdom. AZD3965 is proposed, via lactate transport modulation, to kill tumor cells reliant ...on glycolysis. We investigated the therapeutic potential of AZD3965 in small cell lung cancer (SCLC) seeking rationale for clinical testing in this disease and putative predictive biomarkers for trial use.
AZD3965 sensitivity was determined for seven SCLC cell lines, in normoxia and hypoxia, and for a tumor xenograft model. Proof of mechanism was sought via changes in intracellular/tumor lactate. Expression of MCT1 and related transporter MCT4 was assessed by Western blot analysis. Drug resistance was investigated via MCT4 siRNAi and overexpression. The expression and clinical significance of MCT1 and MCT4 were explored in a tissue microarray (TMA) from 78 patients with SCLC.
AZD3965 sensitivity varied in vitro and was highest in hypoxia. Resistance in hypoxia was associated with increased MCT4 expression. In vivo, AZD3965 reduced tumor growth and increased intratumor lactate. In the TMA, high MCT1 expression was associated with worse prognosis (P = 0.014). MCT1 and hypoxia marker CA IX expression in the absence of MCT4 was observed in 21% of SCLC tumors.
This study provides a rationale to test AZD3965 in patients with SCLC. Our results suggest that patients with tumors expressing MCT1 and lacking in MCT4 are most likely to respond.
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