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At least 163 records · Page 9Linked to original sources

Postcolposcopy management strategies for women referred with low-grade squamous intraepithelial lesions or human papillomavirus DNA-positive atypical squamous cells of undetermined significance: a two-year prospective study.

OBJECTIVE: This study was undertaken to compare postcolposcopy management strategies for women referred for low-grade squamous intraepithelial lesions (LSIL) or oncogenic human papillomavirus (HPV) DNA-positive atypical squamous cells of undetermined significance (ASCUS), with cervical intraepithelial neoplasia (CIN) grade 1 or less found at initial colposcopy. STUDY DESIGN: A 2-year prospective follow-up of 1539 women was designed to assess the percentage sensitivity of different postcolposcopy management strategies to detect subsequent CIN grade 2 or 3 and percentage referral to repeat colposcopy. RESULTS: HPV testing at 12 months was sensitive (92.2%) for detection of CIN grade 2 or 3 with a referral rate to repeat colposcopy of 55.0%. Repeat semiannual cytology with referral to colposcopy at an ASCUS threshold demonstrated similar sensitivity (88.0%) but with a higher rate of referral to colposcopy (63.6%). Combining cytology and HPV testing did not increase sensitivity and hurt specificity. Baseline viral load and colposcopic impression were not helpful. CONCLUSION: The most efficient test for identifying women with CIN grade 2 or 3 after colposcopy might be an HPV test alone at 12 months.

Adolescent↗

Differing response rates and survival between squamous and non-squamous non-small cell lung cancer. Comparison of CAP versus MAP.

One hundred and thirty patients with advanced non-small cell lung cancer were treated in a randomized study with either CAP (cyclophosphamide, doxorubicin, and cisplatin) or MAP (mitomycin C, doxorubicin, and cisplatin). Among all patients, regardless of cell type, the regression rate was slightly higher for MAP (46%) than CAP (34%) but no differences were detected in time to progression and overall survival. However, differences were apparent by treatment when patients were divided into two groups: squamous cell (SQC) and non-squamous cell (non-SQC). MAP, compared to CAP, was associated with a significantly superior regression rate (60% vs. 33%), time to progression, and overall survival in SQC. On the other hand, CAP, compared to MAP, was associated with a significantly longer overall survival in non-SQC. This apparent difference among subtypes of non-small cell lung cancer in response to chemotherapy regimens differing only in one drug, if confirmed, will need to be kept in mind in designing future studies.

Adult↗

Squamous cell carcinoma antigen, circulating immune complexes, and immunoglobulins in monitoring squamous cell carcinoma of head and neck: a study of the hellenic co-operative oncology group (HeCOG).

This study investigates the clinical utility of squamous cell carcinoma antigen (SCC-Ag), circulating immune complexes (CIC), and immunoglobulins (IgA, IgG, IgM) in the diagnosis, monitoring, and prognosis of 117 squamous cell carcinoma of the head and neck (SCC-HN) patients having local and/or systemic treatment. Serum marker levels were measured in a prospective study. SCC-Ag was positive in 28.2% of patients, the CIC in 63.2%, the IgA in 11.1%, the IgG in 15.4%, and the IgM in 9.44%. Statistically significant correlation was found between the initial SCC-Ag levels and tumor localization, whereas the CIC levels were increasing significantly with progressing disease stages. It was also found that the significant decrease of SCC-Ag, IgA, and CIC levels at the end of treatment was correlated with an increased incidence of disease-free status. The initial values of IgG and the disease stage were significantly correlated with a favorable treatment outcome. The pretreatment elevated SCC-Ag and IgM serum values showed a significant trend to predict a disease progression. Using a Cox proportional hazards model the IgG serum values, the primary site, and the disease stage were significant predictors for time to progression. The significant decrease of SCC-Ag, IgA, and CIC values at the completion of treatment was correlated with an increased incidence of disease-free status. This study indicates that only the estimation of SCC-Ag and in some degree the IgM and/or IgG is a potential tool for monitoring the efficacy of treatment or disease recurrence in SCC-HN.

Adult↗

Relationship between telomerase activation and HPV 16/18 oncogene expression in squamous intraepithelial lesions and squamous cell carcinomas of the uterine cervix.

SILs (squamous intraepithelial lesions) comprise a wide spectrum of clinically and biologically heterogeneous lesions ranging from benign proliferations to precancerous lesions. Telomerase activation plays a critical role in cellular immortalization and might be important for malignant progression. The viral oncogenes E6 and E7 are the principal transforming genes of high-risk HPVs and are important in HPV-associated immortalization and neoplastic transformation. In this study we investigated the relationship between telomerase activity, telomerase RNA, and HPV 16/18 oncogene expression in low- and high-grade SILs and SCCs (squamous cell carcinomas) of the cervix uteri. Telomerase activity was examined by the TRAP-assay and expression of the telomerase RNA (hTR) and HPV 16/18 E6/E7 oncogenes by RNA/RNA-in situ hybridization (ISH). The associated HPV-type was determined by PCR. Telomerase activity was observed in 25/29 (86%) SCCs, 31/41 (76%) high-grade SILs, 6/14 (43%) low-grade SILs, and 1/28 (3.6%) normal cervical tissues. Expression of hTR and viral oncogenes increased significantly with histopathologic severity of the lesion (p < 0.0001). A correlation was found between telomerase activity and intensity of viral oncogene expression. These findings suggest that telomerase activation occurs early in cervical carcinogenesis and is predominantly found in high-grade SILs and cervical SCCs. Our findings support current experimental data that suggest that telomerase is at least partially activated by viral oncogenes of high-risk HPV types. Telomerase activity with concomitant strong viral oncogene expression might therefore characterize a subset of lesions that are at risk for malignant progression.

Carcinoma, Squamous Cell↗

The role of pretreatment squamous cell carcinoma antigen level in locally advanced squamous cell carcinoma of the uterine cervix treated by radiotherapy.

The purpose of this study was to determine the pretreatment serum squamous cell carcinoma antigen (SCC-ag) level as a generally applicable measurement in predicting and estimating the treatment outcome of patients with locally advanced SCC of the cervix. Three hundred fifty-two patients with stage IIB-IVA SCC of the cervix were managed with both external irradiation and high-dose rate intracavitary brachytherapy. A significantly higher median SCC-ag was seen in association with increasing stage, tumor size, and lymph node involvement. The difference in disease-free survival (DFS) between stages IIB and III patients was not statistically significant with SCC-ag level <2 ng/mL. In multivariate analysis, median SCC-ag level (> or =6.0 ng/mL) and lymph node metastases had significant independent effects on absolute survival and DFS. A direct linear relationship (y=-2.932x+ 84.896) existed between the median SCC-ag of groups distributed by pretreatment prognostic factors and the 5-year DFS rate. The 5-year DFS rate as a function of SCC-ag level defined by cervix size, lymph node status, and hydronephrosis was obtained from a formula combining risk scores and the baseline survival function. From the obtained formulas, we can objectively estimate the treatment outcome in patients with locally advanced squamous cell cervical cancer.

Adult↗

Expression of c-erbB2 and c-myc in squamous epithelia and squamous cell carcinomas of the head and neck and the lower female genital tract.

Normal tongue and cervical mucosa, premalignant cervical and vulvar lesions, primaries and metastases of squamous cell carcinomas from the oral, laryngeal, cervical and vulvar mucosa were analyzed for c-erbB2 and c-myc transcription with northern-blots using 32P single-stranded RNA probes. Transcription of c-erbB2 and c-myc could be detected for almost all tissues including normal samples. A slightly enhanced transcription level was found in three cervical intraepithelial neoplasias of Grade III (CIN III) but in none of the malignant lesions. Increased transcription of c-myc was observed in premalignancies and malignancies. It was more frequent in oral and laryngeal squamous cell carcinomas (SCC) (8 of 9 cases) than in genital SCC (3 of 11 cases) or premalignancies (3 CIS of 14 CIN/VIN). No relationships of c-myc enhanced transcription level with tumor grading and staging were noticed. Thus, mere oncogene expression is a widespread phenomenon in tissues of different histogenesis and quantitative analysis is necessary prior to ascribe any diagnostic or prognostic relevance. Moreover, the frequency of tumors with enhanced transcription may vary for phenotypically closely related tumors of different organs.

Adult↗

Squamous cell carcinoma related oncogene/DCUN1D1 is highly conserved and activated by amplification in squamous cell carcinomas.

Chromosomal amplification at 3q is common to multiple human cancers, but has a specific predilection for squamous cell carcinomas (SCC) of mucosal origin. We identified and characterized a novel oncogene, SCC-related oncogene (SCCRO), which is amplified along the 3q26.3 region in human SCC. Amplification and overexpression of SCCRO in these tumors correlate with poor clinical outcome. The importance of SCCRO amplification in malignant transformation is established by the apoptotic response to short hairpin RNA against SCCRO, exclusively in cancer cell lines carrying SCCRO amplification. The oncogenic potential of SCCRO is underscored by its ability to transform fibroblasts (NIH-3T3 cells) in vitro and in vivo. We show that SCCRO regulates Gli1--a key regulator of the hedgehog (HH) pathway. Collectively, these data suggest that SCCRO is a novel component of the HH signaling pathway involved in the malignant transformation of squamous cell lineage.

Animals↗

Clinical evaluation of squamous cell carcinoma antigen in squamous cell carcinoma arising in mature cystic teratoma of the ovary.

We attempted to assess the clinical utility of squamous cell carcinoma antigen (SCC) for detecting squamous cell carcinoma arising in mature cystic teratoma of the ovary. SCC in serum from 16 patients with this malignancy and from 56 patients with mature cystic teratoma without malignancy was measured using radioimmunoassay. Serum SCC levels exceeded the cut-off of 2.0 ng/ml in 9 (56%) of the 16 patients with malignancy. This rate was significantly higher than that in the patients with nonmalignant mature cystic teratoma (9 to 56, 16%; p < 0.01). The positive rate for SCC was as low as 30% for stage I cancer. All cases in which the tumor size was > 500 cm3 had a positive response for SCC, whereas all other cases had a negative response (p < 0.001). SCC is useful as a tumor marker for this malignancy. However, the serum SCC level depends on the tumor volume, so it may not be suitable for early detection of small tumors.

Adolescent↗

Esophageal squamous cell papilloma, suspected of squamous cell carcinoma.

A 46-year-old male without any subjective complaints was diagnosed by radiography as having one polypoid lesion at the distal esophagus. Endoscopy indicated a semipedunculated polyp about 1 cm in size, the specimens of which included atypical cells with a high N/C ratio in the submucosa. Squamous cell carcinoma of the esophagus was suspected. Cytological studies of PAS, CEA and keratin staining to atypical cells were all negative, with Lugol solution staining of the tumor. After polypectomy the lesion was diagnosed as a squamous cell papilloma of the esophagus; and the atypical cells were determined to be immature fibroblasts and/or endothelium.

Carcinoma, Squamous Cell↗

Squamous cell carcinoma antigen in serum for monitoring of head and neck and uterine cervical squamous cell carcinomas after radiotherapy.

Squamous cell carcinoma antigen (SCC-A) in serum was serially measured during follow-up of 96 squamous cell carcinoma patients (75 head and neck cancers and 21 uterine cervical cancers), treated with radiotherapy. In 27 of the patients with head and neck cancer and in 12 of those with cervical cancer SCC-A had also been measured before radiotherapy. In this head and neck carcinoma group, the median level of SCC-A was 1.3 (95% CI: 1.2-1.9) ng/ml before radiotherapy and 1.4 (CI: 1.1-1.5) ng/ml after radiotherapy. In the cervical carcinoma group, the median SCC-A decreased significantly (p < 0.001) from a pretreatment value of 7.5 (CI: 3.8-26.3) ng/ml to a posttreatment value of 0.9 (CI: < 0.5-1.8) ng/ml. In the total group of 75 head and neck cancers 21 relapses occurred and in 4 of these the relapse was detected at a clinically silent stage by an elevation of serum SCC-A. The same was true for 4 of the 9 relapses that occurred in the total group of uterine cervical cancer. The study suggests that serum SCC-A may be useful for posttreatment monitoring of patients with uterine cervix cancer while its value in head and neck cancer probably is more marginal.

Adult↗

Is the human papillomavirus test in combination with the Papanicolaou test useful for management of patients with diagnoses of atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesions?

OBJECTIVE: To determine whether human papillomavirus (HPV) testing is useful in the evaluation of patients diagnosed with atypical squamous cells of undetermined significance (ASCUS)/low-grade squamous intraepithelial lesion (LSIL) and whether the HPV test is appropriate as an alternative screening method. DESIGN: The results of Papanicolaou (Pap) tests and subsequent hybrid capture tube (HCT) II tests for high-risk-type HPV were analyzed for 457 patients. Among these tests, 208 histologic diagnoses were made and correlated with the results of Pap and HPV tests. The sensitivity and specificity of the Pap test, HPV test, and the combined method of Pap and HPV tests to detect cervical intraepithelial neoplasia (CIN) 2/3 and all CIN were also measured. RESULTS: Sixty (63.8%) of 94 women with LSIL and 31 (26.3%) of 118 women with ASCUS tested positive for high-risk HPV. The sensitivity values for Pap tests in detecting all cases of CIN and CIN 2/3 were 91.4% and 92.9%, respectively. The sensitivity values of HCT II tests using the high-risk probe for detecting all cases of CIN and CIN 2/3 were 62.6% and 88.1%, respectively. Biopsies confirmed that 10 (22.7%) of 44 LSIL patients with high-risk HPV had CIN 2/3, but only 1 (4.5%) of 22 LSIL patients without high-risk HPV had CIN 2/3. CONCLUSION: Testing for high-risk HPV with the HCT II test is useful in the detection of CIN 2/3 in LSIL groups and in the selection of patients for colposcopy in ASCUS groups, but it is not suitable for cervical cancer screening tests.

Biopsy↗

Carcinoembryonic antigen, squamous cell carcinoma antigen, CYFRA 21-1, and neuron-specific enolase in squamous cell lung cancer patients.

BACKGROUND: Carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC-Ag), and CYFRA 21-1 are the most useful markers for non-small cell lung cancer (NSCLC), but neuron-specific enolase (NSE) is a tumor maker of choice for SCLC. The determination of NSE in NSCLC could allow selection of patients with neuroendocrine features. NSCLC patients whose tumors have neuroendocrine properties may be more responsive to chemotherapy; however, these tumors have been reported to be more aggressive. Tumor markers are not suitable for diagnosis; their principal applications are in monitoring of therapy and prognosis. METHODS: Tumor markers were measured in 200 untreated patients with squamous cell lung cancer (SQC) and a reference group (n = 220; 124 healthy persons and 96 patients with nonmalignant lung disease). CEA and SCC-Ag were measured by microparticle enzyme immunoassays on Abbott AxSYM and IMx analyzers. CYFRA 21-1 and NSE were measured by electrochemiluminescence immunoassays on the Roche Elecsys 2010. RESULTS: CEA, SCC-Ag, CYFRA 21-1, and NSE were increased above the cutoffs in 26%, 32%, 67%, and 28% of tested patients, respectively. The area under the ROC curve for CYFRA 21-1 was higher than those for CEA, SCC-Ag, and NSE (SQC vs controls). CYFRA 21-1 and CEA were significantly higher in advanced SQC than in early stages of disease (P <0.0001 and P <0.0004, respectively). In multivariate analysis of survival, CYFRA 21-1 was an independent but nonspecific prognostic factor in the operable group of SQC patients, whereas NSE was an independent prognostic factor in the advanced stages of disease. CONCLUSION: CYFRA 21-1 is an independent prognostic factor in earlier stages and NSE in the advanced stages of SQC.

Antigens, Neoplasm↗

The role of novel oncogenes squamous cell carcinoma-related oncogene and phosphatidylinositol 3-kinase p110alpha in squamous cell carcinoma of the oral tongue.

PURPOSE: Amplification at chromosome 3q26.3 is a common and crucial event in head and neck squamous cell carcinoma (HNSCC), impacting significantly on tumor progression and clinical outcome. Two novel oncogenes, namely squamous cell carcinoma (SCC)-related oncogene (SCCRO) and PIK3CA (gene encoding phosphatidylinositol-3 kinase catalytic alpha-polypeptide), have been identified as targets of 3q26.3 amplification. This study aimed to delineate the role of SCCRO and PIK3CA in the pathogenesis of oral tongue SCC. EXPERIMENTAL DESIGN: The association between gene copy number for SCCRO and PIK3CA measured by fluorescence in situ hybridization and level of mRNA expression quantitated by real-time reverse transcription-PCR was assessed in a panel of human HNSCC cell lines. In addition, gene expression in 49 consecutive primary SCCs of the oral tongue was determined and correlated with clinicopathological characteristics and outcome. RESULTS: The mRNA level of SCCRO and PIK3CA was significantly correlated to the gene copy number in nine HNSCC cell lines. In addition, the expression level of SCCRO and PIK3CA was significantly greater in malignant tissues compared with those in histologically normal mucosae (2.17- and 2.46-fold, respectively; P < 0.001). Matched tumor normal control analysis revealed that 24.5 and 69.4% of patients expressed high levels of SCCRO and PIK3CA, respectively. Univariate analyses demonstrated that SCCRO overexpression correlated with nodal metastases (P = 0.05) and advanced stage (P = 0.02), whereas PIK3CA overexpression was associated with vascular invasion (P = 0.04). Only SCCRO overexpression was associated with disease-specific (P = 0.04) and overall survival (P = 0.02). Furthermore, SCCRO overexpression remained an independent predictor for cervical nodal metastasis on multivariate regression analysis (chi(2) likelihood ratio = 4.38; P = 0.04). CONCLUSIONS: Although both SCCRO and PIK3CA may play a role in the pathogenesis of oral tongue SCC through amplification at 3q26, SCCRO appears to be a significant predictor of regional metastasis and may be a marker for tumor aggressiveness and clinical outcome.

Adult↗

Cisplatin activates survival signals in UM-SCC-23 squamous cell carcinoma and these signal pathways are amplified in cisplatin-resistant squamous cell carcinoma.

cis-Diaminodichloroplatinum (II) (cisplatin) is one of the most effective anticancer drugs and is widely used for the treatment of squamous cell carcinoma (SCC). However, its efficacy is often limited due to the development of resistance. Although several factors implicated in cisplatin resistance have been identified, the resistance mechanisms in detail are not fully understood yet. In the present study, we have examined the implication of survival signaling pathways in cisplatin-resistance. Cisplatin induced activation of Ras and its downstream effector kinases, Raf/MEK/ERK in UM-SCC-23 human squamous cell carcinoma, suggesting that this anticancer drug activates survival signal pathway in addition to apoptosis signals. In cisplatin-resistant UM-SCC-23 in culture, which we have established, the protein levels of Ras, Raf-1 and MEK were drastically elevated compared to parent UM-SCC-23, and ERK and Akt signals were constitutively activated. U0126, an inhibitor for MEK and LY294002, an inhibitor for phosphatidylinositol 3-kinase (PI3K), sensitized resistant UM-SCC-23 to cisplatin-induced cell death. These results indicate that Raf/MEK/ERK and PI3K/Akt signal cascades may play a considerable role in cisplatin resistance in SCC.

Antineoplastic Agents↗

[Use of high-risk human papillomavirus DNA testing to deal with atypical squamous cells undetermined significance and low squamous intraepithelial lesion].

OBJECTIVE: To explore the role of high-risk human papillomavirus (HPV) DNA testing in improvement of recognition of cervical intraepithelial lesions (CIN) 2, 3 or cervical cancer confirmed by biopsy in women with abnormal cervical cytology including atypical squamous cells undetermined significance (ASC-US) and low squamous intraepithelial lesion (LSIL). METHODS: Total 940 patients with abnormal cervical liquid-based cytology including ASC-US and LSIL were included in this study. Hybrid capture II assay was applied in the high-risk HPV detection. The cervical pathologic diagnoses were obtained under colposcopy guided biopsy. RESULTS: Of the 940 cases, 497 were ASC-US, and 443 LSIL. With pathological diagnosis of cervical biopsy, 417 cases were chronic inflammation, 315 condyloma, 124 CIN 1, 65 CIN 2, 19 CIN 3 or cervical cancer. The positive rate of high-risk HPV DNA in groups of ASC-US and LSIL were 59.6% and 84.9%, respectively. In each group of abnormal cytology, detection rates of CIN 2, 3 or cervical cancer in patients with positive HPV DNA were 8.8% and 14.1%, respectively, which were higher than those with negative HPV DNA (0.2% and 6.0%, P < 0.05). In group of ASC-US, high-risk HPV DNA test had a negative predictive value of 99.5%; detection rates of CIN 2, 3 or cervical cancer in patients with HPV DNA virus load 1-9.99 and > or = 10 was 1.6% and 10.7%, respectively. CONCLUSION: High-risk HPV DNA test were helpful to improve the detection rates of CIN 2, 3 or cervical cancer in patients with ASC-US.

Carcinoma, Squamous Cell↗

The outcome of patients with advanced pure squamous or mixed squamous and transitional urothelial carcinomas following platinum-based chemotherapy.

BACKGROUND: There is limited information about the benefit from systemic chemotherapy in non-pure Transitional Cell Carcinomas (TCCs) of the urothelial tract. In this study the efficacy of platinum-based chemotherapy in patients with pure squamous or mixed carcinomas was retrospectively analysed and compared with that in pure TCCs. PATIENTS AND METHODS: Analysis included 446 consecutive patients treated with platinum-based chemotherapy for advanced or metastatic urothelial cancer. There were 389 (87%) patients with pure TCC, 15 (3.5%) with pure Squamous Cell Carcinomas (SCC) and 42 (9.5%) patients had mixed histology (TCC+SCC) tumors. RESULTS: There were no statistically significant differences in baseline characteristics (gender, PS, haemoglobin, sites of metastases) although disease in the pelvis was more frequent in mixed tumors than in pure TCCs (46% vs. 30%, p = 0.034). Median survival for patients with TCC histology was 11.3 months, for SCC patients 13.6 months and 10.4 months for patients with mixed histology (p = 0.720). Response rates were 44% for patients with TCC, 27% for patients with SCC and 34% for mixed histology patients (p = 0.210). Multivariate analysis showed that presence of visceral metastases and poor performance status, were associated with worse prognosis in mixed histology tumors. CONCLUSION: Non-transitional histology does not predict for an inferior survival after platinum-based chemotherapy for advanced urothelial carcinoma. Well-known prognostic factors in transitional cell carcinomas were also associated with prognosis in mixed carcinomas.

Antineoplastic Combined Chemotherapy Protocols↗

[Clinical and fundamental study of a squamous cell carcinoma related antigen (SCC-RA) for esophageal squamous cell carcinoma].

SCC-RA is one of the fractions of TA-4, extracted and purified from uterine cervical squamous cell carcinoma. I studied SCC-RA in order to evaluate its significance as a tumor marker for esophageal carcinoma. In 32 of 75 (42.7%) esophageal cancer patients, serum SCC-RA was positive. As compared with IAP and CEA, SCC-RA was the best marker to monitor esophageal cancer. SCC-RA positive patients tended to die earlier than negative ones, and it was considered to be one of the prognostic factors. In the immunohistochemical study using anti SCC-RA monoclonal antibody, both the normal epithelium and the carcinoma tissue reacted with SCC-RA. In the carcinoma tissue. SCC-RA reactivity was observed in 27 of 31 specimens (87%). However there was no correlation among the reactivity, the serum level and clinical stage. Furthermore, I studied the relationship between the tumor growth and the serum SCC-RA levels in the nude mice bearing human esophageal squamous cell carcinoma xenografts. The SCC-RA levels in mice sera gradually increased and they correlated well to the tumor volume. In conclusion, SCC-RA reflected the tumor volume and clinical stage, and SCC-RA is useful for monitoring esophageal cancer patients.

Antigens, Neoplasm↗