p16 and p53 are frequently altered intracellular pathways in cancers. We investigated the aberrant expression of p16 and its relationship with p53 and HPV status in primary non-small-cell lung ...carcinoma.
Lung tumor tissue microarray (n = 163), immunohistochemical study of p16 and p53, and HPV
hybridization were analyzed.
p16 and p53 were detected in 50.7 and 57.3% of adenocarcinoma (ADCs; n = 75), and 35.2 and 63.6% of squamous cell carcinoma (n = 88). HPV was detected in 16 and 10.2% of ADC and squamous cell carcinoma. In ADCs, p16 positive tumors demonstrated a favorable median overall survival time of 60.9 months, compared with p16 negative tumors of 46.9 months (p < 0.05). Furthermore, we did not find significant relationships between p16 expression and HPV status, nor with p53 expression.
p16 play an unique role in lung cancer survival. The mechanism of p16 needs to be further studied.
Background:
Bronchoalveolar lavage (BAL) is a specific type of air-way fluid. It is a commonly used clinical specimen for the diagnosis of benign diseases and cancers of the lung. Although previous ...studies have identified several disease-associated proteins in the BAL, the potential utility of BAL in lung cancer is still not well-studied. Based upon the fact that the majority of secreted proteins are glycoproteins, we have profiled
N
-glycoproteins in BAL collected from lung cancers, and investigated the expression of glycoproteins such as the matrix
N-
glycoprotein, periostin, in lung cancers.
Methods:
BAL specimens (
n
= 16) were collected from lung cancer patients, and analyzed using mass spectrometry-based quantitative
N
-glycoproteomic technique. Additional BAL specimens (
n
= 39) were independently collected to further evaluate the expression of periostin by using an enzyme-linked immunosorbent assay (ELISA).
Results:
A total of 462 glycoproteins were identified in BAL samples using
N
-glycoproteomic technique, including 290 in lung adenocarcinoma (ADC,
n
= 5), 376 in squamous cell carcinoma (SQCC,
n
= 4), 309 in small cell lung carcinoma (SCLC,
n
= 4), and 316 in benign lung disease (
n
= 3). The expressions of several glycoproteins were elevated, including 8 in ADC, 12 in SQCC, and 17 in SCLC, compared to benign BALs. The expression of periostin was detected in all subtypes of lung cancers. To further investigate the expression of periostin, an ELISA assay was performed using additional independently collected BALs (
n
= 39) The normalized levels of periostin in benign disease, ADC, SQCC, and SCLC were 255 ± 104 (mean ± SE) and 4,002 ± 2,181, 3,496 ± 1,765, and 1,772 ± 1,119 ng/mg of total BAL proteins.
Conclusion:
Our findings demonstrate that proteomic analysis of BAL can be used for the study of cancer-associated extracellular proteins in air-way fluid from lung cancer patients.
Lung cancer is the leading cause of cancer‐related deaths in the United States. Approximately 40–60% of lung cancer patients present with locally advanced or metastatic disease at the time of ...diagnosis. Lung cancer development and progression are a multistep process that is characterized by abnormal gene and protein expressions ultimately leading to phenotypic change. Glycoproteins have long been recognized to play fundamental roles in many physiological and pathological processes, particularly in cancer genesis and progression. In order to improve the survival rate of lung cancer patients, the discovery of early diagnostic and prognostic biomarkers is urgently needed. Herein, we reviewed the recent technological developments of glycoproteomics and published data in the field of glycoprotein biomarkers in lung cancer, and discussed their utility and limitations for the discovery of potential biomarkers in lung cancer. Although numerous papers have already acknowledged the importance of the discovery of cancer biomarkers, the systemic study of glycoproteins in lung cancer using glycoproteomic approaches is still suboptimal. Recent development in the glycoproteomics will provide new platforms for identification of potential protein biomarkers in lung cancers.
Immunohistochemical expression of GATA-3 is seen predominantly in non-neoplastic bladder and breast epithelium and their respective carcinomas; however, data on expression in normal and lesional ...trophoblastic tissues are limited. Immunohistochemical staining for GATA-3 was assessed in a range of normal/lesional trophoblastic tissues and tumors in the differential diagnosis (n=445), including nonmolar products of conceptions/second and third trimester placentas/ectopic pregnancies, hydatidiform moles, placental site nodules, normal/exaggerated implantation sites, choriocarcinomas, epithelioid trophoblastic tumors, placental site trophoblastic tumors, atypical smooth muscle tumors (including leiomyosarcoma), and cervical and pulmonary squamous cell carcinomas. The extent of expression (0 to 4+) and intensity (weak to strong) were recorded. All cases with developing trophoblast/non-neoplastic trophoblastic proliferation and 81% of trophoblastic neoplasms were positive. Of all non-neoplastic trophoblast cell types, expression was observed in cytotrophoblast in 89% of cases, syncytiotrophoblast in 50%, intermediate trophoblast in 100%, and villous trophoblastic columns in 100%. Increasing gestational age was associated with a decrease in extent/intensity of expression in non-neoplastic cytotrophoblast and syncytiotrophoblast, whereas intermediate trophoblast maintained diffuse and strong expression from early to late gestation (P<0.0001). Eighty-nine percent of normal/exaggerated implantation sites showed 3+ or 4+ expression, whereas staining in 55% of placental site nodules was 1+ or 2+. Staining for GATA-3 was present in 78% of choriocarcinomas, 95% of epithelioid trophoblastic tumors, and 71% of placental site trophoblastic tumors. Although the number of choriocarcinomas and placental site trophoblastic tumors that showed a spectrum of expression ranging from negative to diffuse was relatively evenly distributed, 81% of epithelioid trophoblastic tumors had 3+ or 4+ staining. None of the atypical smooth muscle tumors and 3% of squamous cell carcinomas were positive, all of which exhibited weak staining. We conclude that GATA-3 is frequently expressed in normal and lesional trophoblastic tissues. It is also differentially expressed in intermediate trophoblast and cytotrophoblast/syncytiotrophoblast, which varies according to time during pregnancy. This study expands the spectrum of neoplasms known to express GATA-3. Thus, recognition of expression in trophoblastic tumors is important, because it can present a diagnostic pitfall in the assessment of suspected metastatic bladder or breast carcinomas involving the gynecologic tract. In the evaluation of diagnostically problematic tumors for which trophoblastic neoplasms are in the differential diagnosis, such as leiomyosarcoma and squamous cell carcinoma, GATA-3 can be included as part of an immunohistochemical panel particularly when other trophoblastic markers are either not available or yield ambiguous results.
Background
Fine needle aspiration (FNA) biopsy plays a critical role in the diagnosis and staging of lung primary and metastatic lung carcinoma. Accurate subclassification of adenocarcinoma (ADC) ...and/or squamous cell carcinoma (SqCC) is crucial for the targeted therapy. However, the distinction between ADC and SqCC may be difficult in small FNA specimens. Here, we have retrospectively evaluated the utility of TTF-1, Napsin A, CK7, P63 and CK5/6 immunohistochemical (IHC) markers in the distinguishing and subclassification of ADC and SqCC.
Methods
A total of 246 FNA cases were identified by a computer search over a two-year period, including 102 primary NSCLC and 144 primary NSCLC which had metastasized to other sites. The immunostaining patterns of TTF-1, Napsin A, CK7, P63 and CK5/6 were correlated with the histological diagnosis of the tumor.
Results
In 72 primary ADCs, TTF-1, Napsin A and CK7 showed a sensitivity and specificity of 84.5%/96.4%, 92.0%/100%, and 93.8%/50.0%. In 30 primary SqCCs, CK5/6 and P63 showed a sensitivity and specificity of 100%/77.8% and 91.7%/78.3%. In 131 metastatic ADCs, Napsin A showed the highest specificity (100%), versus TTF-1 (87.5%) and CK7 (25%) but decreased sensitivity (67.8% versus 86.9% and 100%); whereas in 13 metastatic SqCCs, CK5/6 and P63 showed a sensitivity/specificity of 100%/84.6% and 100%/68.4%. Bootstrap analysis showed that the combination of TTF-1/CK7, TTF-1/Napsin A and TTF-1/CK7/Napsin A had a sensitivity/specificity of 0.960/0.732, 0.858/0.934, 0.972/0.733 for primary lung ADCs and 0.992/0.642, 0.878/0.881, 0.993/0.618 for metastatic lung ADCs.
Conclusions
Our study demonstrated that IHC markers had variable sensitivity and specificity in the subclassification of primary and metastatic ADC and SqCC. Based on morphological findings, an algorithm with the combination use of markers aided in the subclassification of NSCLCs in difficult cases.
Prostate cancer, bladder cancer, and renal cancers are major urogenital cancers. Of which, prostate cancer is the most commonly diagnosed and second leading cause of cancer death for men in the ...United States. For urogenital cancers, urine is considered as proximate body fluid to the tumor site for developing non-invasiveness tests. However, the specific molecular signatures from different urogenital cancers are needed to relate changes in urine to various cancer detections. Herein, we utilized a previously published C4-Tip and C18/MAX-Tip workflow for enrichment of glycopeptides from urine samples and evaluated urinary glycopeptides for its cancer specificity. We analyzed 66 urine samples from bladder cancer (n = 27), prostate cancer (n = 4), clear cell renal cell carcinoma (ccRCC, n = 3), and benign plastic hyperplasia (BPH, n = 32) and then compared them with a previous publication that reported glycopeptides associated with aggressive prostate cancer (Gleason score ≥ 8). We further demonstrated the cancer specificity of the glycopeptides associated with aggressive prostate cancer. In this study, a total of 33 glycopeptides were identified to be specifically differentially expressed in prostate cancer compared to other urogenital cancer types as well as BPH urines. By cross-comparison with our previous urinary glycoproteomic dataset for aggressive prostate cancer, we reported a total of four glycopeptides from glycoproteins DSC2, MGAM, PIK3IP1, and CD55, commonly identified to be prostate cancer-specific. Together, these results deepen our understanding of the urinary glycoproteins associated with urogenital cancer types and expand our knowledge of the cancer specificity of urinary glycoproteins among urogenital cancer progression.
Summary In primary lung adenocarcinoma, EGFR and KRAS mutations are found in approximately 10% to 20% and 20% to 30%, respectively. Few studies have investigated these mutations in metastases. ...Patients with EGFR mutations have a 70% to 80% response rate to tyrosine-kinase inhibitors therapy and a longer progression-free survival rate in contrast to patients with KRAS mutations that are associated with virtually no response tyrosine-kinase inhibitors. In this study, we have investigated EGFR and KRAS mutations in metastatic lung adenocarcinoma. Using Johns Hopkins Hospital archives, 1966 lung adenocarcinomas were found from January 2007 to May 2010. A total of 60 metastatic adenocarcinomas (28 cytologic and 32 surgical cases) with EGFR and KRAS studies were identified. In addition, 18 cases of primary and matched metastases were also included. Exons 18 to 21 of EGFR and exon 2 of KRAS (codons 12 and 13) were sequenced. In our study, EGFR and KRAS mutations were found in 21.7% (13 of 60 cases) and 28.3% (17 of 60 cases), respectively, and occurred more often with advanced stage of primary tumors. KRAS mutations were associated with poor prognosis and occurred exclusively in smokers in comparison with EGFR mutation. Of 9 pairs, mutations were concordant in 77.8%; 1 pair displayed acquisition of KRAS mutation, whereas 1 pair showed loss of EGFR mutation in the corresponding metastasis. Our findings suggest that EGFR and KRAS status should be tested in metastasis regardless of known mutations of the primary tumor. Additional studies are needed to further investigate the mechanisms of discordances in metastatic tumors.
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