Pathology Oncology Research

Our medical research library holds 12 studies published in Pathology Oncology Research (2010–2023). Each entry links to the study's record on PubMed and, where there is one, to the publisher's page and a free full text. 12 have an abstract, the authors' own summary as PubMed records it: open "Abstract" to read it.

About the journal

• Publisher: Frontiers Media S. A
• Published: 1995 to the present, Switzerland
• Language: English
• ISSN: 1219-4956 (print), 1532-2807 (electronic)
• Its record in the NLM Catalog

2020s

• Clinical and pathological observation of conversion therapy for malignant peritoneal mesothelioma: a case report and literature review. M. Deng, X. Zhang, C. Xu, et al. 2023;29:1611577. Review · Case report PubMed · Publisher · Free full text

  Abstract

  Background: Malignant mesothelioma (MM) is a tumor originating from the pleura, peritoneum, or pericardial cavity. It is divided into diffuse and localized malignant mesothelioma, with four subtypes in diffuse MM: epithelioid, sarcomatoid, desmoplastic, and biphasic, with biphasic being less common. The onset of this tumor is insidious, and the prognosis is extremely poor in some cases, with a median survival of 6-18 months and no standard treatment options in the past. Aims: We report a case of peritoneal malignant mesothelioma that was successfully treated with transformative therapy. We also review the literature in the hope of providing reference for the treatment and pathological diagnosis of such patients. Methods: The case of the peritoneal malignant mesothelioma was processed and reported in the routine manner for biopsy specimens at different stages. Results and conclusion: We report a case of a malignant tumor originating in the hepatorenal recess, which was diagnosed as biphasic malignant mesothelioma through a biopsy. Immunohistochemical testing showed PD-L1 expression. After multidisciplinary discussion, the patient received transformative treatment, including a trial of combined immunotherapy. The tumor significantly shrank, and the patient obtained a chance for curative surgical resection. Microscopic examination showed significant collagenization in the lesion area, with almost no residual tumor. After 19 months of comprehensive treatment, the patient developed multiple fluffy opacities under the pleura of both lungs. Transthoracic core needle biopsy under CT guidance, the pathology showed organizing pneumonia, considering it as delayed interstitial pneumonitis due to immunotherapy based on previous treatment history. Successful comprehensive treatment was achieved for this case of peritoneal malignant mesothelioma, and the patient has been alive without evidence of disease for 33 months, with long-term follow-up. In this process, the pathologist had three opportunities for pathological diagnosis, which required understanding the patient's medical history, being attentive to the clinical purpose of the specimen, and providing accurate responses to morphological changes at different stages, along with corresponding descriptions and diagnoses to provide effective information for clinical treatment.

  Copyright © 2024 Deng, Zhang, Xu, Luo, Chen, Zhou and Hou.

• Diagnostic Utility of BAP1, EZH2 and Survivin in Differentiating Pleural Epithelioid Mesothelioma and Reactive Mesothelial Hyperplasia: Immunohistochemical Study. S.A. Hakim, H.H. Abou Gabal. 2021;27:600073. PubMed · Publisher · Free full text

  Abstract

  Background: Epithelioid mesothelioma (EM) is the commonest subtype of malignant pleural mesothelioma. Its histopathological discrimination from reactive mesothelial hyperplasia (RMH) could be challenging. Thus, an immunohistochemical panel is mandatory for better discrimination. BAP1 is a newly identified diagnostic marker whose loss is specific to malignant mesothelioma. EZH2 overexpression is reported in different cancers, but its relation to BAP1 in malignant mesothelioma has not been fully understood. Survivin expression is said to be significantly higher in EM than in non-neoplastic pleural tissue, but its diagnostic utility as an immunohistochemical marker has not been thoroughly investigated in this field. To the best of our knowledge, no previous studies have been conducted to assess the diagnostic accuracy of the combined use of these three nuclear markers (BAP1, EZH2 and Survivin) in discriminating pleural EM from RMH. Methods: This retrospective study includes two groups: 81 cases of pleural EM and 67 cases of RMH, retrieved from the archives of Pathology Department of Ain Shams University Hospitals and Ain-Shams University Specialized Hospital during the period from January 2016 to December 2019. An immunohistochemical study was performed using BAP1, EZH2 and Survivin antibodies. Results: There were highly statistically significant relations between study groups as regards the studied markers (p = 0.001 for each). The specificity was 100% for all combinations of immunohistochemical markers. Sensitivity of any combination of the immunohistochemical markers used in this study was found to be higher than the sensitivity of any of these markers used individually. The combination of all three markers showed the highest diagnostic accuracy (95.9%) and the highest sensitivity (92.6%). However, the combination of Survivin and EZH2 yielded the same diagnostic accuracy and sensitivity. Conclusion: Adding EZH2, Survivin and BAP1 to the diagnostic IHC panel for differentiating pleural EM and RMH could enhance diagnostic sensitivity. Moreover, Survivin is a potentially promising marker in this context, especially when combined with EZH2.

  Copyright © 2021 Hakim and Abou Gabal.

• Aquaporins 1, 3 and 5 in Different Tumors, their Expression, Prognosis Value and Role as New Therapeutic Targets. M.S. Moosavi, Y. Elham. 2020;26(2):615-625. Review PubMed · Publisher

  Abstract

  All different types of metabolism of tumors are dependent on the flow of water molecules through the biological membrane, where fluid transfer interceded by aquaporins (AQPs) are the basis means for water entrance into the cells or outside them. Aquaporins play other roles including cellular migration, cellular expansion and cellular adhesion facilitation. Therefore, regulators of AQPs may be useful anticancer agents. Medline, Scopus, Embase, and Web of Sciences were searched. From among the papers found, 106 were related to the subject. All of the examined cancers in relation to AQP1 included adenoid cystic carcinoma, bladder, breast, cervical, colon, colorectal, hepatocellular, lung, ovarian, plural mesothelioma, prostate, renal cell carcinoma and squamous cell carcinoma. All of the studied cancers in relation with AQP3 included gastric, breast, prostate, lung, pancreas, skin, bladder, squamous cell carcinoma, cervical, adenoid cystic carcinoma, colon, colorectal, ovarian, and hepatocellular cancers and with regard to AQP5 were lung, squamous cell carcinoma, ovarian, adenoid cystic carcinoma, breast, colon, colorectal, hepatic, pancreas, gallbladder, prostate, and gastric cancers. Over or under-expression of AQP1, 3 and is exist in the mentioned cancers across different studies. Over-expression of AQP1, AQP3 and AQP5 is clearly associated with carcinogenesis, metastasis, reduced survival rate, lymph node metastasis, poorer prognosis, and cellular migration. Also, cancer treatments in relation to these markers suggest AQP reduction during the treatment.

• Monoclonal Caveolin 1 Expression in the Differential Diagnosis of Malignant Pleural Mesothelioma and Pulmonary Adenocarcinoma: Is it Useful?. Z. Bozdag, E. Tutar, O.F. Dizibuyuk, et al. 2020;26(3):1651-1656. PubMed · Publisher

  Abstract

  In this study we aim to demonstrate the value of monoclonal Caveolin 1 expression in distinguishing between malignant pleural mesothelioma and pulmonary adenocarcinoma. Total of 129 cases, consisting of 68 cases of malignant pleural mesothelioma (51 epitheloid, 12 biphasic, and 5 sarcomatoid type) and 61 cases of pulmonary adenocarcinoma were examined and stained with monoclonal Caveolin-1. Caveolin 1 expression with a membranous and /or cytoplasmic pattern was detected only in 32.35% (n:22/68) of malignant pleural mesothelioma and 6.5% (n:4/61) of pulmonary adenocarcinoma cases. This finding suggests that the choice of poly/monoclonal antibody for Caveolin 1 in the differential diagnosis of malignant pleural mesothelioma and pulmonary adenocarcinoma is important.

• The Investigation of Lipoxygenases as Therapeutic Targets in Malignant Pleural Mesothelioma. L. Oguh-Olayinka, V. Agarwal, D. Ranatunge, et al. 2020;26(2):985-995. PubMed · Publisher · Free full text

  Abstract

  Advanced malignant pleural mesothelioma (MPM) has an extremely poor prognosis with limited chemotherapy options, therefore the identification of new therapeutic targets would aid in disease management. Arachidonic acid is metabolised by cyclooxygenase and lipoxygenase enzymes. The lipoxygenase isoenzymes 5-LOX and 12-LOX have been implicated in carcinogenesis. We aimed to examine 5-LOX and 12-LOX protein expression in a large retrospective series of mesothelioma samples. Further to this, the in vitro cytotoxic effects of lipoxygenase pathway inhibitors were investigated in mesothelioma cells. Archival samples from 83 patients with MPM were examined by immunohistochemistry for expression of the 5-LOX and 12-LOX proteins. The MTS assay was used to assess cell viability following 72 h treatment with the lipoxygenase pathway inhibitors baicalein, licofelone, MK-886 and zileuton in the MPM cell lines NCI-H2052, NCI-H2452 and MSTO-211H. Positive 12-LOX protein expression was recorded in 69/83 (83%) and positive 5-LOX expression was observed in 56/77 (73%) of MPM tissue samples. Co-expression of 5-LOX with 12-LOX was seen in 46/78 (58%) of MPM samples. Positive expression of 5-LOX, 12-LOX and COX-2 proteins was identified in the NCI-H2052, NCI-H2452 and MSTO-211H MPM cell lines. Baicalein (12-LOX and 15-LOX inhibitor) was effective in 3/3 MPM cell lines at low concentrations with an IC50 range of 9.6 μM to 20.7 μM. We have demonstrated that the 5-LOX and 12-LOX proteins are expressed in a significant proportion of MPM samples (73% and 83% respectively) and may represent novel therapeutic targets in this disease. We have demonstrated that the inhibition of the LOX pathway using baicalein may be effective as a novel treatment for MPM, however further human pharmacokinetic studies are required in order to establish whether the concentration used in vitro is clinically achievable.

2010s

• Signal Transducer and Activator of Transcription 1 (STAT1) Knock-down Induces Apoptosis in Malignant Pleural Mesothelioma. L. Arzt, I. Halbwedl, M. Gogg-Kamerer, et al. 2017;23(3):595-605. PubMed · Publisher

  Abstract

  Malignant pleural mesothelioma (MPM) is the most common primary tumor of the pleura. Its incidence is still increasing in Europe and the prognosis remains poor. We investigated the oncogenic function of signal transducer and activator of transcription 1 (STAT1) in MPM in more detail. A miRNA profiling was performed on 52 MPM tissue samples. Upregulated miRNAs (targeting SOCS1/3) were knocked-down using miRNA inhibitors. mRNA expression levels of STAT1/3, SOCS1/3 were detected in MPM cell lines. STAT1 has been knocked-down using siRNA and qPCR was used to detect mRNA expression levels of all JAK/STAT family members and genes that regulate them. An immunohistochemical staining was performed to detect the expression of caspases. STAT1 was upregulated and STAT3 was downregulated, SOCS1/3 protein was not detected but it was possible to detect SOCS1/3 mRNA in MPM cell lines. The upregulated miRNAs were successfully knocked-down, however the expected effect on SOCS1 expression was not detected. STAT1 knock-down had different effects on STAT3/5 expression. Caspase 3a and 8 expression was found to be increased after STAT1 knock-down. The physiologic regulation of STAT1 via SOCS1 is completely lost in MPM and it does not seem that the miRNAs identified by now, do inhibit the expression of SOCS1. MPM cell lines compensate STAT1 knock-down by increasing the expression of STAT3 or STAT5a, two genes which are generally considered to be oncogenes. And much more important, STAT1 knock-down induces apoptosis in MPM cell lines and STAT1 might therefore be a target for therapeutic intervention.

• The Role of CD90 in the Differential Diagnosis of Pleural Malignant Mesothelioma, Pulmonary Carcinoma and Comparison with Calretının. N. Sahin, A.N. Akatli, M.R. Celik, et al. 2017;23(3):487-491. PubMed · Publisher

  Abstract

  Pleural Malignant Mesothelioma (MM) is a fatal disease that has been associated with asbestos exposure. Differential diagnosis between the pleural infiltration of pulmonary carcinomas and MM is rather difficult particularly for epitheloid type mesothelioma.We aimed to investigate the utility of CD90, a cancer stem cell marker, in the differential diagnosis of MM and lung carcinoma, its prognostic significance and compare its value with that of Calretinin. Ninety pathology specimens including MM (n:30), pulmonary adenocarcinoma (n:30) and pulmonary squamous cell carcinoma (n:30) were used in this study. Immunohistochemical comparision of CD 90 and Calretinin was made in all groups. Calretinin was positive in 20 cases with MM (64.5 %), and was negative in 10 (32.3 %). CD 90 was positive in 25 of these cases (80 %) and negative in 5 (16 %). On the other hand pulmonary adenocarcinomas and squamous cell carcinomas showed positivity with CD90, 63,6 % and 73 %, respectively. We think that CD 90 has no place in the differential diagnosis between mesothelioma and pulmonary carcinoma because of the low specificity in spite of the high sensitivity.

• Turning back the Wheel: Inducing Mesenchymal to Epithelial Transition via Wilms Tumor 1 Knockdown in Human Mesothelioma Cell Lines to Influence Proliferation, Invasiveness, and Chemotaxis. T. Plönes, M. Fischer, K. Höhne, et al. 2017;23(4):723-730. PubMed · Publisher

  Abstract

  Malignant pleural mesothelioma (MPM) is a highly aggressive tumor that arises from the surface of the pleura and is associated with a history of asbestos exposure. The tumor is characterized by a strong local invasiveness and a poor response to any single modality therapy. Therefore clinical outcome of patients with MPM is poor and median survival time of untreated patients with MPM is 7 months from initial diagnosis. The Wilms Tumor Protein 1 (WT1) is a transcription factor which is highly expressed by MPM and is involved in cellular development and survival. We evaluated the role of WT1 in two human MPM cell lines (MSTO and H2052) expressing high levels of WT1. We performed a knockdown of WT1 using siRNA. Knockdown of WT1 was confirmed by Westernblotting. After knockdown of WT1 we investigated the effect on proliferation, chemoresistance, chemotaxis and migration. We could demonstrate that knockdown of WT1 suppresses chemoresistance in both cell lines compared with control (scrambled siRNA). Additionally, WT1 knockdown reduces proliferation, chemotaxis and invasiveness of mesothelioma cell lines. WT1 reduces malignancy of malignant mesothelioma cell lines and might be a new molecular target in mesothelioma therapy. Further investigations are needed to discover the mechanisms of chemoresistance depending on WT1.

• BAP1 protein is a progression factor in malignant pleural mesothelioma. L. Arzt, F. Quehenberger, I. Halbwedl, et al. 2014;20(1):145-51. PubMed · Publisher

  Abstract

  Human malignant pleural mesothelioma (MPM) is an aggressive cancer due to former asbestos exposure with little knowledge about prognostic factors of outcome and resistance to conventional therapy. BRCA1-associated protein 1 (BAP1) is a tumor suppressor gene that is frequently lost in MPM. Germline mutations of BAP1 predispose to several different tumors including malignant mesothelioma. Our study aimed to clarify if asbestos exposure has an influence on BAP1 expression and if BAP1 expression could be used as a prognostic factor of outcome. An immunohistochemical staining for BAP1 was performed on 123 MPM tissue samples and the expression levels have been correlated with asbestos exposure and overall survival time. BAP1 expression was not associated with asbestos exposure but we detected a significant effect of BAP1 expression on overall survival time--the higher the BAP1 expression (non-mutated BAP1), the shorter the overall survival. BAP1 mutation has been linked to non-asbestos induced familial mesotheliomas, which usually belong to the long survivor group and BAP1 is most probably functioning differently than in sporadic cases. Further investigations need to be performed to characterize the BAP1 mutations and to identify the BAP1 downstream targets in MPM.

• Expression of thyroid transcription factor-1 in malignant pleural effusions. A. Khoor, A.L. Byrd-Gloster, S.V. Nicosia. 2011;17(2):263-7. PubMed · Publisher

  Abstract

  Separating adenocarcinoma of the lung from non-pulmonary adenocarcinoma or malignant mesothelioma is difficult, especially in cytology specimens. Consequently, it is important to identify markers that may facilitate this distinction. Thyroid transcription factor-1 (TTF-1) is a homeodomain containing transcription factor expressed selectively in the thyroid, lung, and diencephalon. TTF-1 is also expressed in adenocarcinomas of the lung and is widely used as a pulmonary adenocarcinoma marker in surgical specimens. However, the utility of TTF-1 has rarely been investigated in cytology. In this study, we evaluated the expression of TTF-1 in malignant pleural effusions. The primary tumors included 26 pulmonary adenocarcinomas, 26 non-pulmonary adenocarcinomas (13 breast, 5 ovarian, 2 gastric, 2 prostatic, 1 esophageal, 1 colonic, 1 pancreatic and 1 renal) and 4 malignant mesotheliomas. Immunocytochemistry was performed on sections of cell blocks, using a mouse monoclonal TTF-1 antibody (clone 8G7G3/1) and a biotin-streptavidin detection system. Nuclear immunoreactivity for TTF-1 was detected in 19 pulmonary adenocarcinomas. All non-pulmonary adenocarcinomas and malignant mesotheliomas were negative. These data indicate that TTF-1 maintains its sensitivity (73%) and specificity (100%) in cell block preparations and is useful in separating adenocarcinoma of the lung from non-pulmonary adenocarcinoma and malignant mesothelioma in cytology specimens.

• Primary peritoneal serous papillary carcinoma: a clinical and pathological study. Q. Liu, J.X. Lin, Q.L. Shi, et al. 2011;17(3):713-9. PubMed · Publisher

  Abstract

  Primary peritoneal serous papillary carcinoma (PPSPC) is a rare primary tumor of the peritoneum that found predominantly in elderly and post-menopausal women. The aim of our study is to review the clinical and pathologic information of 22 patients, and then try to summarize clinical behavior and pathological characteristics of PPSPC, in order to be better recognized of this entity in future. We retrospectively reviewed the data from 22 patients with PPSPC treated at our hospital from 1992 to 2008. All paraffin blocks were recut for periodic acid-Schiff diastase and immunohistochemical staining for CD15, cytokeratin7(CK7), cytokeratin20(CK20), S-100 protein, carcinoembryonic antigen (CEA), CA125, estrogen receptor(ER) and progesterone receptor(PR). The median age of the patients at the time of surgical staging was 56 years (range, 32-77 years). The most common presenting symptoms were abdominal distension (59.1%) and ascites (63.6%). Pretreatment CA125 levels were significant elevated in 90.5% patients. Optimal debulking was performed in 18 patients. All patients were consequently treated with platinum-based chemotherapy. Response to treatment is promising, and the median overall survival of all patients was 21.0 months (95% CI 16.9, 25.1 months). The positive rate of immunohistochemical staining was CD15 95.5%, CK7 90.9%, S-100 protein 68.2%, CA125 59.1%, CK20 31.8%, ER 31.8%, CEA 27.3% and PR 9.1%, respectively. Gynecologist should be aware of PPSPC when abdominal distension, gross ascites and a raised level of CA125 in women without ovarian enlargement. Immunohistochemical staining might be helpful as accessory criteria for the differential diagnosis among the PPSPC, peritoneal malignant mesothelioma (PMM), primary epithelial ovarian carcinoma (PEOC) and peritoneal carcinomatosis from the gastrointestinal tumors (SPCGT). Cytoreductive surgery combined with pre/postoperative platinum-based chemotherapy may be effective for PPSPC patients.

• Impact of tumor angiogenesis in peritoneal mesothelioma after radical cytoreduction and hyperthermic intraperitoneal chemotherapy. T.C. Chua, P. Yao, J. Akther, et al. 2010;16(2):217-22. PubMed · Publisher

  Abstract

  Peritoneal mesothelioma is one of the peritoneal surface malignancies where long-term survival is a reality after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Tumor angiogenesis has been shown to be of prognostic significance on survival in mesothelioma. We investigated the impact of survival of patients with peritoneal mesothelioma following CRS and HIPEC to determine the impact of tumor angiogenesis on survival after this radical surgical treatment. Paraffin sections of 23 patients who were treated with CRS and HIPEC were retrieved for immunohistochemical analysis. The immunostaining was performed using monoclonal mouse anti-human antibodies (VEGF-C and CD31) on an autostainer (Autostainer Plus; Dako, Inc.). The intensity of the stains were quantified using the Image-Pro Plus (IPP) 4.5 (Media Cybernetics, Silver Spring, MD). VEGF expression and microvessel density (MVD) using CD31 staining were studied. The median survival was 94 months with a 3-year survival rate of 51%. There was no impact on patient's age, sex, peritoneal cancer index, tumor histopathology and survival outcomes between patients with low or high MVD and VEGF expression. After CRS and HIPEC, our results demonstrate that the prognostic significance of tumor angiogenesis is negated, highlighting the potential importance of other co-contributory mechanisms in mesotheliomagenesis and undergoing radial treatment.

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