The promising role of mucin 4 in association with D2-40 immunohistochemistry in differentiating pleural sarcomatoid mesothelioma from lung sarcomatoid carcinoma

AbstractMalignant pleural mesothelioma (MPM) is an aggressive neoplasm originating from the pleura. Non-epithelioid (biphasic and sarcomatoid) MPM are particularly resistant to therapy. We investigated the role of the GITR-GITRL pathway in mediating the resistance to therapy. We found that GITR and GITRL expressions were higher in the sarcomatoid cell line (CRL5946) than in non-sarcomatoid cell lines (CRL5915 and CRL5820), and that cisplatin and Cs-137 irradiation increased GITR and GITRL expressions on tumor cells. Transcriptome analysis demonstrated that the GITR-GITRL pathway was promoting tumor growth and inhibiting cell apoptosis. Furthermore, GITR+ and GITRL+ cells demonstrated increased spheroid formation in vitro and in vivo. Using patient derived xenografts (PDXs), we demonstrated that anti-GITR neutralizing antibodies attenuated tumor growth in sarcomatoid PDX mice. Tumor immunostaining demonstrated higher levels of GITR and GITRL expressions in non-epithelioid compared to epithelioid tumors. Among 73 patients uniformly treated with accelerated radiation therapy followed by surgery, the intensity of GITR expression after radiation negatively correlated with survival in non-epithelioid MPM patients. In conclusion, the GITR-GITRL pathway is an important mechanism of autocrine proliferation in sarcomatoid mesothelioma, associated with tumor stemness and resistance to therapy. Blocking the GITR-GITRL pathway could be a new therapeutic target for non-epithelioid mesothelioma.

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The predictive role of neutrophil-to-lymphocyte ratio in the outcomes of patients with sarcomatoid carcinoma of oral cavity

European Archives of Oto-Rhino-Laryngology ◽

10.1007/s00405-021-06800-x ◽

2021 ◽

Author(s):

Roshankumar Patil ◽

Prakash Pandit ◽

Vijay Palwe ◽

Rahul Patil ◽

Sucheta Gandhe ◽

...

Keyword(s):

Oral Cavity ◽

Sarcomatoid Carcinoma ◽

Neutrophil To Lymphocyte Ratio ◽

Lymphocyte Ratio ◽

Predictive Role

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Carcinosarcoma/sarcomatoid carcinoma of the urinary bladder with features of malignant fibrous histiocytoma: the role of p53 in growth of the tumor

Türk Üroloji Dergisi/Turkish Journal of Urology ◽

10.5152/tud.2011.033 ◽

2011 ◽

Vol 37 (2) ◽

pp. 172-176

Author(s):

Ozden Tulunay ◽

Aysegul Yalcinkaya ◽

Evren Suer ◽

Cagatay Gogus ◽

Semih Tangal ◽

...

Keyword(s):

Urinary Bladder ◽

Malignant Fibrous Histiocytoma ◽

Fibrous Histiocytoma ◽

Sarcomatoid Carcinoma

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Management of the Uncommon Bladder Cancers: A Single-Center Experience over 10 Years

Advances in Urology ◽

10.1155/2020/7563703 ◽

2020 ◽

Vol 2020 ◽

pp. 1-7

Author(s):

Youssef Kadouri ◽

Salim Lachkar ◽

Hamza Dergamoun ◽

Hachem El Sayegh ◽

Lounis Benslimane ◽

...

Keyword(s):

Sarcomatoid Carcinoma ◽

Epidermoid Carcinoma ◽

Therapeutic Management ◽

Concomitant Radiochemotherapy ◽

Total Cystectomy ◽

Therapeutic Modalities ◽

Single Center Experience ◽

Wide Range ◽

One Year

Background. Under the name of uncommon bladder cancers are gathered rare histological entities which represent less than 5% of bladder tumors. There is not a clear and consensual therapeutic management for these entities. Purpose. To review a single-institution 10-year experience with rare form of bladder cancers detailing the diagnosis, treatment, and patient outcome. Materials and Methods. We performed a retrospective review of 27 medical records of rare bladder cancer form treated at our center between February 2006 and February 2015. The clinicopathologic features are reported with emphasis on treatment and survival. Results. Mean patient age was 65.5 ± 20 yr and 70% of patients were males. Smoking background was found in 16 cases, chronic bladder irritation factors were found in 12 cases, and past urinary tract infection was found in 11 cases. The main symptom was total hematuria (93%) causing an anemia in 16 cases. The two mean histological forms were epidermoid carcinoma (37%) and adenocarcinoma (22%). 26% of patients were found to have extended invasive tumors (T4) at diagnosis. Metastatic disease was confirmed in 8 cases. Our patients were managed by a wide range of therapeutic modalities as total cystectomy with bilateral lymph node dissection (63%), palliative chemotherapy (30%), or concomitant radiochemotherapy (7%). 55.6% of patients were alive one year after diagnosis. Epidermoid carcinoma has the best prognosis followed by leiomyosarcoma and sarcomatoid carcinoma. Neuroendocrine carcinoma has the worst outcome. The overall 5-year survival rate is 33.3%. Conclusion. The rarity and small size of these tumors justify the absence of clear and consensual therapeutic management. No role of total cystectomy concerning the conclusions could be drawn but elements suggest this may be the treatment of choice. The highly aggressive nature of those lesions justifies an aggressive and fast therapy when feasible which gives the best outcomes.

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Value of immunohistochemistry in the differential diagnosis of pleural sarcomatoid mesothelioma from lung sarcomatoid carcinoma

Histopathology ◽

10.1111/j.1365-2559.2009.03298.x ◽

2009 ◽

Vol 54 (6) ◽

pp. 667-676 ◽

Cited By ~ 41

Author(s):

Yukio Takeshima ◽

Vishwa J Amatya ◽

Kei Kushitani ◽

Mayumi Kaneko ◽

Kouki Inai

Keyword(s):

Differential Diagnosis ◽

Sarcomatoid Carcinoma ◽

Sarcomatoid Mesothelioma

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MUC4, a novel immunohistochemical marker identified by gene expression profiling, differentiates pleural sarcomatoid mesothelioma from lung sarcomatoid carcinoma

Modern Pathology ◽

10.1038/modpathol.2016.181 ◽

2017 ◽

Vol 30 (5) ◽

pp. 672-681 ◽

Cited By ~ 15

Author(s):

Vishwa Jeet Amatya ◽

Kei Kushitani ◽

Amany Sayed Mawas ◽

Yoshihiro Miyata ◽

Morihito Okada ◽

...

Keyword(s):

Gene Expression ◽

Gene Expression Profiling ◽

Expression Profiling ◽

Sarcomatoid Carcinoma ◽

Immunohistochemical Marker ◽

Sarcomatoid Mesothelioma

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Utility of Immunohistochemistry for MUC4 and GATA3 to Aid in the Distinction of Pleural Sarcomatoid Mesothelioma From Pulmonary Sarcomatoid Carcinoma

Archives of Pathology & Laboratory Medicine ◽

10.5858/arpa.2019-0647-oa ◽

2020 ◽

Author(s):

Simone B.S.P. Terra ◽

Anja C Roden ◽

Marie Christine Aubry ◽

Eunhee S. (Joanne) Yi ◽

Jennifer M. Boland

Keyword(s):

Clinical Features ◽

Sarcomatoid Carcinoma ◽

Male Predominance ◽

Tissue Sections ◽

Immunohistochemical Markers ◽

Muc4 Expression ◽

Gata3 Expression ◽

Pulmonary Sarcomatoid Carcinoma ◽

Tumor Types ◽

Sarcomatoid Mesothelioma

Context.— Distinguishing pulmonary sarcomatoid carcinoma from pleural sarcomatoid mesothelioma is challenging because of overlapping histology, immunophenotype, and clinical features. Reliable immunohistochemical markers to aid in this distinction would be very valuable. Recent studies have proposed that MUC4 expression is common in sarcomatoid carcinoma but not in sarcomatoid mesothelioma, with the converse pattern reported for GATA3. Objective.— To further explore the utility of MUC4 and GATA3 in distinguishing pulmonary sarcomatoid carcinoma from sarcomatoid mesothelioma. Design.— Well-characterized cases of sarcomatoid carcinoma (n = 32) and sarcomatoid mesothelioma (n = 64) were included. Diagnoses were confirmed by thoracic pathologists with incorporation of immunophenotype, clinical, and radiographic features. Whole-tissue sections were stained for GATA3 and MUC4. Results.— Patients with sarcomatoid carcinoma and sarcomatoid mesothelioma had similar mean age and male predominance. GATA3 was positive in 63 of 64 sarcomatoid mesotheliomas (98%; 42 diffuse, 16 patchy, 5 focal), and 15 of 32 sarcomatoid carcinomas (47%; 3 diffuse, 8 patchy, 4 focal). MUC4 was positive in 2 of 64 sarcomatoid mesotheliomas (3%; 1 patchy, 1 focal), and in 12 of 32 sarcomatoid carcinomas (38%; 5 diffuse, 6 patchy, 1 focal). Conclusions.— Diffuse GATA3 expression favors sarcomatoid mesothelioma over sarcomatoid carcinoma, which rarely shows diffuse expression (sensitivity and specificity of diffuse staining 66% and 94%, respectively). Focal and patchy GATA3 expression is observed in both tumor types, and therefore is not helpful in this distinction. Sensitivity of MUC4 for sarcomatoid carcinoma was low in our cohort, positive in only 38% with frequent patchy staining, but it was quite specific.

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