An overview of the rare parotid gland cancer

Cancer of the parotid gland is relatively rare, but carries poor prognosis owing to its prevailing distant metastases. In addition to the disease's basic epidemiology and pathology, we review some current discoveries of its tumorigenesis molecular mechanism. Based on published salivary gland cancer clinical trial data, non-surgical antitumor efficacies amongst a range of chemotherapy, radiation, and concurrent therapy regimens are compared. We also present the current development status of novel radiation therapy and targeted therapeutics, focusing on intensity-modulated radiation therapy (IMRT), and epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) blockages, which are showing promise for improving parotid gland cancer management

Monitoring and Determining Mitochondrial Network Parameters in Live Lung Cancer Cells.

Mitochondria are dynamic organelles that constantly fuse and divide, forming dynamic tubular networks. Abnormalities in mitochondrial dynamics and morphology are linked to diverse pathological states, including cancer. Thus, alterations in mitochondrial parameters could indicate early events of disease manifestation or progression. However, finding reliable and quantitative tools for monitoring mitochondria and determining the network parameters, particularly in live cells, has proven challenging. Here, we present a 2D confocal imaging-based approach that combines automatic mitochondrial morphology and dynamics analysis with fractal analysis in live small cell lung cancer (SCLC) cells. We chose SCLC cells as a test case since they typically have very little cytoplasm, but an abundance of smaller mitochondria compared to many of the commonly used cell types. The 2D confocal images provide a robust approach to quantitatively measure mitochondrial dynamics and morphology in live cells. Furthermore, we performed 3D reconstruction of electron microscopic images and show that the 3D reconstruction of the electron microscopic images complements this approach to yield better resolution. The data also suggest that the parameters of mitochondrial dynamics and fractal dimensions are sensitive indicators of cellular response to subtle perturbations, and hence, may serve as potential markers of drug response in lung cancer

Cancer-Secreted miR-105 Destroys Vascular Endothelial Barriers to Promote Metastasis

SummaryCancer-secreted microRNAs (miRNAs) are emerging mediators of cancer-host crosstalk. Here we show that miR-105, which is characteristically expressed and secreted by metastatic breast cancer cells, is a potent regulator of migration through targeting the tight junction protein ZO-1. In endothelial monolayers, exosome-mediated transfer of cancer-secreted miR-105 efficiently destroys tight junctions and the integrity of these natural barriers against metastasis. Overexpression of miR-105 in nonmetastatic cancer cells induces metastasis and vascular permeability in distant organs, whereas inhibition of miR-105 in highly metastatic tumors alleviates these effects. miR-105 can be detected in the circulation at the premetastatic stage, and its levels in the blood and tumor are associated with ZO-1 expression and metastatic progression in early-stage breast cancer

Expression of cytokeratin 5/6 in epithelial neoplasms: An immunohistochemical study of 509 cases

Cytokeratin 5/6 (CK 5/6) immunoreactivity has been observed in the vast majority of cases of malignant mesothelioma but only rarely in pulmonary adenocarcinomas. Thus, CK 5/6 has been used to distinguish malignant mesothelioma from pulmonary adenocarcinoma. However, the utility of CK 5/6 in distinguishing pleural malignant mesothelioma from pleural metastases from nonpulmonary adenocarcinoma, as well as peritoneal malignant mesothelioma from peritoneal metastatic adenocarcinoma, has not yet been adequately addressed because the tissue expression of CK 5/6 in nonpulmonary neoplasms has not been well defined. We have studied the CK 5/6 expression in 509 cases of various epithelial tumors by immunohistochemistry. We found that the vast majority of cases of squamous cell carcinoma, basal cell carcinoma, thymoma, salivary gland tumor, and biphasic malignant mesothelioma were positive for CK 5/6. In addition, CK 5/6 immunoreactivity was detected in 15 of 24 cases (62%) of transitional cell carcinoma, in 5 of 10 cases (50%) of endometrial adenocarcinoma, in about one third of cases of pancreatic adenocarcinoma (36%) and breast adenocarcinoma (31%), and in one quarter of cases of ovarian adenocarcinomas (25%). Our study confirms the diagnostic utility of CK 5/6 immunohistochemistry in distinguishing biphasic mesothelioma from pulmonary adenocarcinoma but raises caution about its use for the differential diagnosis of pleural or peritoneal malignant mesothelioma versus pleural or peritoneal metastatic nonpulmonary adenocarcinoma, because many types of nonpulmonary adenocarcinomas may be positive for CK 5/6

Immunohistochemical characterization of signet-ring cell carcinomas of the stomach, breast, and colon

We studied the immunophenotype of signet-ring cell carcinoma (SRCC) of the stomach (30 cases), breast (21 cases), and colon (9 cases) with the following expression patterns: (1) breast: consistent, MUC1 (21 [100%]), cytokeratin (CK) 7 (20 [95%]), estrogen receptor (ER; 17 [81%]); infrequent, E-cadherin (6 [29%]), MUC2, MUC5AC, CK20 (1 [5%] each); negative, CDX2 and hepatocyte paraffin 1 (Hep Par 1; 0 [0%] each); (2) gastric: frequent, CDX2 (27 [90%]) and Hep Par 1 (25 [83%]); variable, E-cadherin and CK20 (17 [57%] each), MUC2 and MUC5AC (15 [50%] each), MUC1 (5 [17%]); negative, ER (0 [0%]); and (3) colon: frequent, MUC2 (9 [100%]), CDX2 and MUC5AC (8 [89%] each); infrequent or negative, MUC1 (3 [33%]), Hep Par 1 (2 [22%]), ER (0 [0%]). Immunohistochemical staining distinguished breast from gastric SRCC (ER, MUC1, Hep Par 1, CDX2) and colon SRCC (ER, CDX2, MUC2, and MUC5AC). Gastric and colon SRCCs showed a similar staining pattern for antibodies tested except for Hep Par 1 and CDX2 (gastric, 83% Hep Par 1 positivity and heterogeneous, weak, patchy CDX2 nuclear staining; colon, 22% Hep Par 1 positivity and homogeneous, strong, diffuse CDX2 nuclear staining). About half of the cases of gastric SRCC expressed MUC2 and MUC5AC, whereas virtually all cases of colon SRCC expressed them

Incidental and concurrent malignant lymphomas discovered at the time of prostatectomy and prostate biopsy: A study of 29 cases

The incidence and histologic features of malignant lymphomas discovered at the time of prostate biopsy, transurethral resection, and prostatectomy are not well documented. We searched our surgical pathology files for malignant lymphomas identified from prostate surgical specimens from 1989 to 2004. Of 4,831 cases of prostate specimens (3,405 biopsies, 266 transurethral resections, 1,160 prostatectomies) examined at the City of Hope during this period, 29 cases of malignant lymphomas involving the prostate and pelvic lymph nodes were identified (0.6%). These malignant lymphomas can be divided into two groups: 1) 18 incidental cases (0.37%) without prior history of malignant lymphoma; and 2) 11 cases (0.23%) with concurrent known malignant lymphoma. For the first group, the patients with pelvic node involvement ranged in age from 59 to 78 years (mean, 69.2 years; median, 70 years), and the patients with prostate involvement ranged in age from 45 to 78 years (mean, 64.6 years; median, 67.5 years). For the second group, the patients ranged in age from 53 to 80 years (mean, 66.8 years; median, 69 years). Diagnoses of all cases were confirmed by immunohistochemistry or molecular analysis. Ten of 18 cases in the first group involved pelvic nodes only, and the other 8 cases were primary prostatic lymphoma. Of 18 cases in the first group, 13 were small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL), 3 were marginal zone B-cell lymphoma, and 1 was mantle cell lymphoma. These lymphomas were not readily apparent in most cases by histologic examination, and may be confused with chronic prostatitis when the prostate was involved or with reactive lymphoid hyperplasia when pelvic nodes were involved. Immunohistochemistry and molecular studies may be necessary to confirm the diagnosis. For the second group, prostate and pelvic lymph nodes were involved as part of systemic dissemination of concurrent malignant lymphoma. The diagnosis was usually easily established in these cases. Of 11 cases, 4 were SLL/CLL, 4 were follicular lymphoma, 2 were mantle cell lymphoma, and 1 was diffuse large B-cell lymphoma. Copyright © 2005 by Lippincott Williams & Wilkins

Association of intratubular seminoma and intratubular embryonal carcinoma with invasive testicular germ cell tumors

The classification of intratubular germ cell neoplasia of the testis includes an unclassified type (IGCNU), in addition to various other intratubular lesions that show specific forms of differentiation, such as intratubular seminoma and intratubular embryonal carcinoma. Although IGCNU is recognized as a precursor lesion for testicular germ cell tumors, the relationship between differentiated types of intratubular germ cell neoplasia and invasive germ cell tumors of the testis is not well established. The aim of the present study was to examine the association between invasive testicular germ cell tumors and intratubular neoplastic lesions, with particular emphasis on differentiated types of intratubular germ cell neoplasia. The seminiferous tubules adjacent to 42 testicular germ cell tumors were evaluated for the presence of various forms of intratubular germ cell neoplasia. IGCNU was observed in 37 (88%) of 42 cases, whereas intratubular seminoma and intratubular embryonal carcinoma were seen in 19% and 7% of the cases, respectively. Intratubular seminoma was associated primarily with seminomas or mixed germ cell tumors with a seminomatous component, but was also present in a case of a nonseminomatous germ cell tumor. Intratubular embryonal carcinoma was associated exclusively with nonseminomatous germ cell tumors. All cases of intratubular embryonal carcinoma were identified morphologically and exhibited histologic features corresponding to traditional definitions of this lesion. No examples of intratubular embryonal carcinoma as defined by CD30 expression alone in the absence of an intratubular proliferation were observed. The presence of intratubular seminoma in a nonseminomatous germ cell tumor suggests that it is a true preinvasive lesion rather than a manifestation of intratubular spread of an established invasive seminoma. The low incidence of intratubular embryonal carcinoma supports the theory that most nonseminomatous germ cell tumors evolve initially as seminomas, rather than directly from a differentiated intratubular neoplastic lesion. © 2007 Lippincott Williams & Wilkins, Inc

Hepatocyte antigen as a marker of intestinal metaplasia

Intestinal metaplasia is a histologic hallmark of Barrett\u27s esophagus and chronic gastritis. Intestinal metaplasia may progress to dysplasia or carcinomas without proper treatment. Most cases of intestinal metaplasia are easily recognized on hematoxylin and eosin-stained sections. However, some cases of intestinal metaplasia may be hard to recognize if they lack the characteristic mucin-producing cells and Paneth cells, or if they are small in size. Recently, keratin 7, keratin 20, and MUC2 expression patterns were reported to be useful in confirming the diagnosis of intestinal metaplasia. We studied hepatocyte (Hep) antigen (a hepatocellular antigen mainly expressing in normal and neoplastic hepatic tissues) in 33 cases of Barrett\u27s esophagus (9 cases associated with esophageal adenocarcinoma) and 13 cases of chronic gastritis associated with intestinal metaplasia and gastric adenocarcinoma. Hep monoclonal antibody recognizes intestinal metaplasia in all cases. We also compared expression of Hep with that of keratin 7, keratin 20, and MUC2 in intestinal metaplasia. The specificity and sensitivity of Hep for intestinal metaplasia were higher than that of keratin 7 and keratin 20, or MUC2. We conclude that Hep may be used as a single diagnostic marker for intestinal metaplasia