Mesothelioma: Ordonez NG

Butnor KJ, Sporn TA, Ordonez NG, Anonymous00042. · Department of Pathology, University of Vermont, 111 Colchester Avenue, Burlington, VT 05401, USA. · Hum Pathol. · Pubmed #17276491 No free full text.

Abstract: It has been evident for decades that pathology reports are very variable even within a single institution. Standardization of reporting is the optimal way to ensure that information necessary for patient management, prognostic and predictive factor assessment, grading, staging, analysis of outcomes, and tumor registries is included in pathology reports. In recent years, 2 societies (first the Association of Directors of Anatomic and Surgical Pathology [ADASP] and then the College of American Pathologists [CAP]) have undertaken to publish guidelines for the reporting of common cancers. The CAP assigned multidisciplinary groups of pathologists, surgeons, radiation, and medical oncologists to develop the protocols. Other pathologists and clinicians then reviewed them. After those reviews the protocols were reviewed by multiple CAP committees and finally approved by the Board of Governors. The ADASP, in contrast, chose a pathologist expert in each filed to assemble a group from within the pathology community (with clinician input if desired) to write specific cancer protocols. These were then approved by the ADASP council and subsequently by the membership. Although both societies began the process at approximately the same time, the streamlined approach adopted by the ADASP enabled them to publish years earlier in pathology journals frequented by anatomic pathologists. Although the formats are somewhat different, the contents are essentially the same. The American College of Surgery Commission on Cancer (COC) accredits cancer centers in the United States. Recently, the COC decided to require elements, deemed as essential by the CAP, to be described in all pathology reports in their accredited cancer centers as of January 2004. Importantly, they do not require that the specific CAP protocols or synoptic reports be used. The ADASP has updated all of its protocols to comply with the COC requirements in the form of 37 uniform checklists. The checklists use the staging criteria sited in the American Joint Committee on Cancer 2002 Staging Manual (sixth edition) but include a variety of other references listed in each of the checklists. Moreover, the checklists are formatted for ease of use. They may be used as templates for uniform reporting and are designed to be compatible with voice-activated transcription. The different elements in these revised ADASP diagnostic checklists have been divided into required and optional. The term required in this context only signifies compliance with the COC guidelines. The ADASP realizes that specimens and practices vary, and it will not be possible to report these elements in every case. However, the ADASP hopes that pathologists will find these checklists to be useful in daily clinical practice, while facilitating compliance with the new COC requirements.

Butnor KJ, Ordonez NG. · The University of Vermont, Burlington, VT, USA. · Appl Immunohistochem Mol Morphol. · Pubmed #18528285 No free full text.

Abstract: AIM: To analyze the immunohistochemical expression of uroplakin (URO) in pleural malignant mesothelioma (PMM). METHODS AND RESULTS: We analyzed URO expression in PMM using similar immunohistochemical techniques at 2 separate institutions. At an antibody dilution of 1:10, 0/5 PMMs were immunoreactive for URO. At 1:8, diffuse weak cytoplasmic staining was seen in all 38 PMMs tested, but no membrane staining was observed. Adjacent nontumor tissue and positive control tissue showed cytoplasmic staining of equivalent intensity. Similar staining results were observed in 27 PMMs at a 1:5 dilution. CONCLUSIONS: At an antibody dilution for which positive and negative control tissues stain appropriately, PMM does not stain for URO. At higher antibody concentrations, PMM exhibits nonspecific cytoplasmic staining. We assert that URO is not a useful immunohistochemical marker for the detection of PMM. Further studies addressing whether URO is overexpressed at the mRNA level in PMM are warranted.

Tsao AS, He D, Saigal B, Liu S, Lee JJ, Bakkannagari S, Ordonez NG, Hong WK, Wistuba I, Johnson FM. · Department of Thoracic/Head and Neck Medical Oncology, M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 432, Houston, TX 77030, USA. · Mol Cancer Ther. · Pubmed #17620427 links to  free full text

Abstract: Malignant pleural mesothelioma (MPM) is a deadly disease with few systemic treatment options. One potential therapeutic target, the non-receptor tyrosine kinase c-Src, causes changes in proliferation, motility, invasion, survival, and angiogenesis in cancer cells and may be a valid therapeutic target in MPM. To test this hypothesis, we determined the effects of c-Src inhibition in MPM cell lines and examined c-Src expression and activation in tissue samples. We analyzed four MPM cell lines and found that all expressed total and activated c-Src. Three of the four cell lines were sensitive by in vitro cytotoxicity assays to the c-Src inhibitor dasatinib, which led to cell cycle arrest and increased apoptosis. Dasatinib also inhibited migration and invasion independent of the cytotoxic effects, and led to the rapid and durable inhibition of c-Src and its downstream pathways. We used immunohistochemical analysis to determine the levels of c-Src expression and activation in 46 archived MPM tumor specimens. The Src protein was highly expressed in tumor cells, but expression did not correlate with survival. However, expression of activated Src (p-Src Y419) on the tumor cell membrane was higher in patients with advanced-stage disease; the presence of metastasis correlated with higher membrane (P = 0.03) and cytoplasmic (P = 0.04) expression of p-Src Y419. Lower levels of membrane expression of inactive c-Src (p-Src Y530) correlated with advanced N stage (P = 0.02). Activated c-Src may play a role in survival, metastasis, and invasion of MPM, and targeting c-Src may be an important therapeutic strategy.

Butnor KJ, Sporn TA, Ordonez NG, Anonymous00079. · Department of Pathology, University of Vermont, Burlington, VT, USA. · Virchows Arch. · Pubmed #17334801 No free full text.

This publication has no abstract.

Rice DC, Erasmus JJ, Stevens CW, Vaporciyan AA, Wu JS, Tsao AS, Walsh GL, Swisher SG, Hofstetter WL, Ordonez NG, Smythe WR. · Department of Thoracic and Cardiovascular Surgery, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA. · Ann Thorac Surg. · Pubmed #16305830 No free full text.

Abstract: BACKGROUND: Extrapleural pneumonectomy for malignant pleural mesothelioma (MPM) is a high-risk procedure, and patients require careful preoperative staging to exclude advanced disease. Computed tomography, magnetic resonance imaging, and positron emission tomography are useful staging modalities, but do not reliably identify contralateral mediastinal involvement or transdiaphragmatic invasion. We evaluated the role of extended surgical staging procedures, which generally includes a combination of laparoscopy, peritoneal lavage, and mediastinoscopy, to more precisely stage patients with MPM. METHODS: One hundred eighteen patients with MPM, deemed clinically and radiologically resectable, underwent extended surgical staging. Mediastinoscopy was performed in 111 patients, laparoscopy in 109 patients, and peritoneal lavage in 78 patients. RESULTS: Ten (9.2%) patients had gross evidence of transdiaphragmatic or peritoneal involvement. Peritoneal lavage was positive for metastatic MPM in 2 (2.6%) patients, neither of whom had obvious transdiaphragmatic invasion. Ipsilateral mediastinal nodes contained metastatic tumor in 10 of 62 (16.1%) patients. Contralateral nodes were positive in 4 of 111 (3.6%) patients. Of the patients who underwent biopsy of both ipsilateral and contralateral mediastinal nodes, and who had complete pathologic staging after extrapleural pneumonectomy (n = 46), 14 (30.4%) had N2-positive nodes. Only 5 of these patients were correctly identified by mediastinoscopy (sensitivity 36%, accuracy 80%). Extended surgical staging identified 16 (13.6%) patients who had contralateral nodal involvement, transdiaphragmatic invasion, or positive peritoneal cytology. CONCLUSIONS: Extended surgical staging defines an important subset of patients with unresectable MPM not identified by imaging. Because of the potential morbidity associated with extrapleural pneumonectomy, we advocate that extended surgical staging be performed in all patients with MPM before resection.

Allen TC, Cagle PT, Churg AM, Colby TV, Gibbs AR, Hammar SP, Corson JM, Grimes MM, Ordonez NG, Roggli V, Travis WD, Wick MR. · Department of Pathology, Baylor College of Medicine, Houston, TX, USA. · Am J Surg Pathol. · Pubmed #15958850 No free full text.

Abstract: Localized malignant mesotheliomas are uncommon sharply circumscribed tumors of the serosal membranes with the microscopic appearance of diffuse malignant mesothelioma but without any evidence of diffuse spread. Little is known about their behavior. We report 23 new cases. The mean age at presentation was 63 years, and the sex ratio was approximately 2:1 (male/female). Twenty-one tumors were pleural and 2 were peritoneal. Sixteen tumors reproduced microscopic patterns of diffuse epithelial mesotheliomas, 6 had mixed epithelial and sarcomatous patterns, and 1 was purely sarcomatous. After surgical excision of the tumor, 10 of 21 patients with follow-up data were alive without evidence of disease from 18 months to 11 years after diagnosis. Patients who died had developed local recurrences and metastases, but none had diffuse pleural spread. Localized malignant mesotheliomas should be separated from diffuse malignant mesotheliomas because of their localized presentation, quite different biologic behavior, and far better prognosis.