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[Effect of expression of gut-enriched Kruppel-like factor on esophageal squamous cancer cells].

Gut-enriched Kruppel-like factor (GKLF) is a newly identified eukaryotic zinc finger protein expressed extensively in the gastrointestinal tract, and its expression is associated with growth arrest. Previous work showed that GKLF expression was down-regulated in esophageal squamous cancer. In the present work, the effects of sense and antisense expression of GKLF on the esophageal squamous cancer cell line EC9706 were observed to get more knowledge of the role of down-regulation of GKLF in the initiation and/or progression of esophageal cancer. Antisense transfection of GKLF gene in EC9706 led to decreased expression of GKLF in the cells, and these cells showed increased cell growth rate, indicating that down-regulation of the GKLF gene might contribute to cellular hyperproliferation. Both increased and decreased expression of GKLF in EC9706 by sense and antisense GKLF expression also led to the decreased adhesion of cells, suggesting a role of GKLF in the metastasis of esophageal squamous cancer. The results demonstrate that down-regulation of GKLF expression in esophageal squamous cancer causes the cancer cells to become hyperproliferative and less adhesive, and suggest that decreased expression of GKLF may contribute to the malignant phenotype of esophageal squamous cancer.

Carcinoma, Squamous Cell↗

[Squamous cell carcinoma of the celiac area. Report of a case and review of the literature].

Primary squamous cell carcinoma of the pancreas or of the stomach is rare and represents a controversial entity. The unusual case of a 50-year-old woman with a large squamous cell carcinoma located in the celiac area and involving liver, stomach and pancreas, is reported here. The patient underwent complete surgical resection. The microscopic diagnosis was well-differentiated squamous cell carcinoma without glandular structure. Following the procedure, search for another possible primary lesion (esophagus, anus, colon, lung, head and neck, pelvic floor) was performed. This search was negative. In this context, final diagnosis was primary gastric or pancreatic squamous cell carcinoma. Local recurrence located in the eso-jejunal anastomosis was discovered three years later. Subsequent radiation combined with chemotherapy was instituted, allowing complete remission. During the subsequent 27-month follow-up, no local or systemic recurrence was observed. Pathogenesis of gastric as well as pancreatic primary squamous cell carcinoma remains obscure and controversial. These tumors usually have a very poor prognosis with rapid vascular and lymphatic involvement. Nevertheless, favorable outcome seems possible, as exhibited in our patient.

Antineoplastic Agents↗

[Expression of apoptosis and proliferation related genes in carcinogenesis of lung squamous cell carcinoma in rats].

BACKGROUND & OBJECTIVE: The activation of caspase-3 protein, located the downstream of apoptosis, is the key of cell apoptosis signal conduction. Caspase-3 is the most important performer in accelerating apoptosis in the caspase family. Much progress has been achieved in the study of caspase-3 and human non-small cell lung cancer. This study was designed to investigate the effect of cellular proliferation and apoptosis related genes caspase-3 and proliferating cell nuclear antigen (PCNA), and to seek whether they could be chosen as molecular biology markers for lung cancer. METHODS: 3-Methylcholanthrene (MCA) and diethyinitrosamine (DEN) were used to induce lung squamous cell carcinoma by intra-left lobar-bronchial instillation in 50 Wistar rats. The other 10 rats instilled with iodized oil were regarded as control group. The expression of caspase-3 and PCNA were evaluated by SP immunohistochemistry during carcinogenesis. TUNEL(TDT-mediated dUTP nick end labeling) method was used to examine apoptotic cells. RESULTS: For the rat bronchial epithelium cells in control group, precancerous lesions, and lung squamous cell carcinoma, positive coefficient values of caspase-3 protein were 3.10+/-0.99, 2.25+/-1.13, and 1.38+/-0.95 on average, respectively; the means of PCNA-labeling index (PCNA-LI)were 14.10+/-5.02, 28.13+/-8.72, and 41.88+/-14.24, respectively; the means of apoptotic index(AI) were 0.60+/-0.52, 2.06+/-0.85, and 2.26+/-1.14, respectively.Significant differences in caspase-3 protein expression were observed between bronchial epithelium in control group and lung squamous cell carcinoma (P< 0.01). Caspase-3 expression was showed stronger in precancerous lesions than that in lung cancer (P< 0.05). Low proliferation index and low AI were detected in rat bronchial epithelium region in control group,which were significant differences in precancerous lesions and lung cancer, respectively (P< 0.01). In 34 rats with lung squamous cell carcinoma, there was negative relationship between caspase-3 and PCNA-LI (r=-0.7306, P< 0.01), so did it in AI and PCNA-LI(r=-0.8127,P< 0.01), but there was no relationship between caspase-3 expression and AI(P >0.05). CONCLUSION: Loss of caspase-3 expression may be associated with the development of lung squamous cell carcinoma in Wistar rats, but it is not associated with AI. PCNA-LI is an important marker for malignant progression of lung cancer.

Animals↗

[The expression of cytokeratin No. 17 in squamous cell cancer of the cervix uteri: an immunohistochemical study of 19 cases].

Monoclonal antibodies E3 against cytokeratin No. 17 were used for immunohistochemical examination of samples from 19 squamous-cell carcinomas of the uterine cervix and 10 cases of squamous-cell metaplasia of the endocervix. The above antibodies selectively labelled reserve cells of the cervical canal mucosa, basal layer of mature metaplastic epithelium and parabasal and basal cells of immature metaplastic squamous epithelium. In large-cell keratinizing, non-keratinizing and small-cell carcinomas, the expression of cytokeratin No. 17 revealed tendency to basal orientation and was in many respects similar to that in metaplastic squamous epithelium. It was suggested that all the squamous-cell carcinomas studied originated from reserve (metaplastic) cells.

Adult↗

[Squamous cell carcinoma of the gallbladder associated with adenocarcinoma in situ: a case report].

Squamous cell carcinoma of the gallbladder associated with adenocarcinoma in situ of the mucosal columnar epithelium is extremely rare. The case presented here is the first to be documented at the Veterans General Hospital-Taipei. In this case, dysplastic columnar epithelium was discovered alongside with squamous cell carcinoma and squamous metaplasia. Focal adenocarcinoma in situ was also identified. The significance of these associated lesions and the histogenesis of squamous metaplasia and squamous cell carcinoma in gallbladder are discussed.

Adenocarcinoma↗

Squamous metaplasia of normal and carcinoma in situ of HPV 16-immortalized human endocervical cells.

The importance of cervical squamous metaplasia and human papillomavirus 16 (HPV 16) infection for cervical carcinoma has been well established. Nearly 87% of the intraepithelial neoplasia of the cervix occur in the transformation zone, which is composed of squamous metaplastic cells with unclear origin. HPV DNA, mostly HPV 16, has been found in 90% of cervical carcinomas, but only limited experimental data are available to discern the role of HPV 16 in this tissue specific oncogenesis. We have initiated in vivo studies of cultured endocervical cells as an experimental model system for development of cervical neoplasia. Using a modified in vivo implantation system, cultured normal endocervical epithelial cells formed epithelium resembling squamous metaplasia, whereas those immortalized by HPV 16 developed into lesions resembling carcinoma in situ. In contrast, their ectocervical counterparts formed well differentiated stratified squamous epithelium and a lesion with mild dysplastic change, respectively. The HPV 16-immortalized cells showed in vivo cytokeratin expression patterns similar to their respective normal counterparts, confirming their different origins. Thus, this study provides direct experimental evidence for the transformation of simple epithelial cells of endocervical origin into stratified squamous metaplasia and indicates the differential susceptibility of endo- and ectocervical epithelial cells for conversion to cancer by HPV 16.

Animals↗

Treatment of cutaneous squamous cell carcinomas by intralesional interferon alfa-2b therapy.

BACKGROUND AND DESIGN: Intralesional recombinant interferon alfa-2b has been shown to be effective in the treatment of actinic keratoses and basal cell carcinomas. This open-label study was designed to evaluate the effectiveness and cosmetic result of this therapy on actinically induced, primary cutaneous squamous cell carcinomas. Thirty-six squamous cell carcinomas (28 invasive lesions and 8 in situ lesions) ranging in size from 0.5 to 2.0 cm in the longest dimension were treated with interferon alfa-2b 1.5 million units injected intralesionally three times per week for 3 weeks. Eighteen weeks following therapy, the treatment sites were excised and examined for histologic evidence of remaining tumor. RESULTS: Thirty-three (97.1%) of 34 evaluable lesions revealed an absence of squamous cell carcinoma histologically after therapy, although three biopsy specimens (8.8%) obtained after treatment showed actinic keratoses, for an overall complete response rate of 88.2%. The lesion not eliminated after treatment was an invasive squamous cell carcinoma. The investigators and patients independently judged 93.9% of cases to have a very good or excellent cosmetic result. Adverse reactions were limited to those influenzalike symptoms well recognized to occur with interferon therapy and these were well tolerated. Only one patient discontinued therapy due to side effects. CONCLUSIONS: This trial demonstrates that intralesional interferon is effective in the treatment of small sun-induced squamous cell carcinomas with well-tolerated side effects and a highly acceptable cosmetic result.

Adult↗

[Significance and expression of vascular endothelial growth factor-C (VEGF-C) in esophageal squamous carcinoma and glioma].

BACKGROUND & OBJECTIVE: The research in recent years has demonstrated that vascular endothelial growth factor-C (VEGF-C) is expressed in certain malignant tumor cells, and up to now VEGF-C is the only growth factor specific for lymphangiogenesis. The relationship between the VEGF-C expression in malignant tumor tissues and lymphatic metastasis is still scarcely reported. This study was designed to compare the VEGF-C expression in human esophageal squamous carcinoma and glioma, and then to analyze the relationship between the VEGF-C expression and tumor lymphatic metastasis. METHODS: The expression of VEGF-C antigen was detected with immunohistochemical method in 72 human esophageal squamous carcinomas (29 cases with lymph node metastasis,43 cases without lymph node metastasis) and 23 human gliomas (diagnosed pathologically as astrocytoma in grades I to IV), followed by the further analysis on the relationship between VEGF-C expression and clinicopathological parameters. RESULTS: The expression of VEGF-C antigen was not found in any gliomas, while the positive VEGF-C expression rate achieved 38.88%(28/72) in the human squamous carcinoma, with 62.07%(18/29) in the cases with lymph node metastasis, 23.26%(10/43) in the cases without lymph node metastasis, 58.82% (20/34) in the T2 and T3 of invasion depth cases, and 21.05%(8/38)in the T1 of invasion depth cases. CONCLUSION: The expression of VEGF-C antigen was significantly associated with lymph node metastasis and invasion depth in esophageal squamous carcinoma. VEGF-C may act as a key factor in the facilitation of lymphatic metastasis in esophageal squamous carcinoma.

Adult↗

[The study of the expression, effect and clinical relationship of TGF-beta 1 in the larynx squamous carcinoma].

OBJECTIVE: This study was to measure the expression of TGF-beta 1 in larynx squamous carcinoma, to investigate the relationship between TGF-beta 1 and pathological grading of tumours, the clinical staging and, through which the effect of TGF-beta 1 on the pathogenesis of the larynx squamous carcinoma was to be known. METHOD: RNA was extracted from the larynx squamous carcinoma tissues of 21 patients and from normal laryngeal tissues of 15 cases. Reverse transcriptional polymerase chain reaction (RT-PCR) was applied to detect the expression of the TGF-beta 1 mRNA. RESULT: Ten of the 21 specimens of the larynx squamous carcinoma showed positive expression of TGF-beta 1 mRNA, then the expression ratio was 47.62%. The expression of TGF-beta 1 mRNA had relationship to the pathological grading and the clinical staging of the larynx carcinoma. CONCLUSION: TGF-beta 1 can be used as a marker to evaluate the progression of laryngeal squamous cell carcinoma.

Adult↗

[Preliminary research of the relationship between overexpression of facilitative glucose transporter-1 and fluorodeoxyglucose uptake in primary human lung squamous cell carcinoma].

OBJECTIVE: To assess the relationship between the overexpression of facilitative glucose transporter-1 (Glut1) and fluorine-18 fluorodeoxyglucose (FDG) uptake in patients with primary lung squamous cell carcinoma. METHODS: From April 1999 to March 2001, 23 patients with lung squamous cell carcinoma were imaged using FDG positron emission tomography (PET) before surgery. Their maximum and mean standard uptake values (SUVmax and SUVmean) of tumor and SUV of the normal lung (SUVlung) were measured. The expression of Glut1 of all the 23 cases was analysed in paraffin sections using SP immunohistochemistry. RESULTS: All the 23 tumors tested were Glut1 positive (69 +/- 18)% of tumor cell area was positive and staining intensity was 4.6 +/- 0.7. All tumors of the patients could be detected by FDG-PET. FDG uptake of tumor was higher than that of normal lung (P < 0.01). SUVmax, SUVmean and SUVlung were 8.33 +/- 4.14, 6.10 +/- 3.00 and 0.38 +/- 0.13 respectively. Correlations were found among Glut1 expression and FDG uptake and tumor size (P < 0.01). CONCLUSIONS: (1) Glut1 overexpression is universal in the lung squamous cell carcinoma. (2) SUV was higher in the lung squamous cell carcinoma than that of the normal lung tissue. (3) Glut1 expression and FDG uptake and tumor size appear to be correlated with each other in patients with lung squamous cell carcinoma.

Aged↗

[Expression and correlation of apoptosis-related gene c-IAP2 and caspase-4 in head and cervical undifferentiation squamous cell carcinoma].

OBJECTIVE: To examine the expression of apoptosis-related genes c-IAP2 and caspase-4 in head and cervical undifferentiation cell carcinoma, as well as to investigate the role and mechanism of the two apoptosis-related genes in head and cervical undifferentiation squamous cell carcinoma. METHOD: Sixty-six historily confirmed specimen of head and cervical undifferentiation squamous cell carcinoma were subjected for immunohistochemical staining to analyze the expression of c-IAP2 and caspase-4, in addition 5 cases of normal nasal mucosa tissue were selected as control. RESULT: 1. Higher level expression of c-IAP2 protein was detected in the head and cervical undifferentiation squamous cell carcinoma specimen compared with normal nasal mucosa(P < 0.05), and the expression of caspase-4 was more deletion in it than in normal nasal mucosa(P < 0.05). 2. The expression of c-IAP2 protein was positive correlation with clinical prognosis, not correlated with clinical staging. The expression of caspase-4 protein was negative correlated with clinical prognosis, not correlated with clinical staging, too. 3. The expression of c-IAP2 was negative correlated with the expression of caspase-4. CONCLUSION: It indicates that in tissue of head and cervical undifferentiation squamous cell carcinoma, c-IAP2 is activated while caspase-4 is restrained. The signal transduction pathway of apoptosis is arrested, leading to surviving of the tumor cells, which maybe directly associated with the developing of head and cervical undifferentiation squamous cell carcinoma, and also with the failure of tumor treatment.

Apoptosis↗

Squamous cell carcinoma of breast--report of two case.

Squamous cell carcinoma is an extremely rare variant of breast cancer. Presence of unequivocal squamous differentiation should be observed to diagnose a case as squamous cell carcinoma of breast since focal squamous metaplasia is frequently seen in common variants of breast carcinoma. We report here two cases of squamous cell carcinoma of breast, one a primary metaplastic type and the other one metastatic from a carcinoma of the cervix.

Breast Neoplasms↗

Lugol staining pattern in background epithelium of patients with esophageal squamous cell carcinoma.

BACKGROUND/AIMS: Squamous cell carcinoma of the esophagus often arises in the setting of chronic esophagitis. We investigated whether chronic esophagitis was associated with carcinogenesis in the esophageal squamous epithelium. METHODOLOGY: Videoendoscopy with Lugol staining was performed in 70 patients with invasive carcinoma of the esophagus. We especially focused the study on background epithelium of the esophagus, then background epithelium was classified into two groups according to differences in Lugol staining patterns. Following Lugol solution spraying, background epithelium showing uniform greenish-brown staining was defined as having a uniform pattern. In contrast, when multiple Lugol-unstained speckles were present throughout the esophagus, the pattern was defined as speckled. Furthermore, we also investigated whether glycogenic acanthosis is present or not in background epithelium. RESULTS: Chronic esophagitis was present in 11 of 70 patients (16%) with invasive carcinoma, indicating a speckled pattern in background epithelium following Lugol solution spraying. The remaining 84% of patients with invasive carcinoma showed normally uniform Lugol staining background epithelium. Glycogenic acanthosis was found in 65 (93%) of 70 patients. CONCLUSIONS: Approximately 80% of patients with esophageal squamous cell carcinoma showed normal Lugol staining of background epithelium. Field carcinogenesis is postulated to be not predominant in the development of esophageal squamous cell carcinoma in our Japanese subjects. In contrast, glycogenic acanthosis of the esophagus was associated with the background epithelium accompanied with esophageal squamous cell carcinoma.

Adult↗

[Clinical analysis of 71 cases of multiple primary cancers in head and neck squamous carcinomas].

OBJECTIVE: To study the location, treatment, life status of multiple primary cancers (MPCs) in head and neck squamous cell carcinomas. METHODS: The clinical data of 71 head and neck squamous carcinoma patients with MPCs were retrospectively analyzed. RESULTS: MPCs were seen in head and neck regions in 27 cases and in remote organs in 42 cases, two of which were triplicate primary cancers. Four cases were synchronous MPCs, including one patient with synchronous triplicate primary cancer. Other 67 cases were heterochronous MPCs, including one patient with heterochronous triplicate primary cancer. Of 67 heterochronous MPCs, the time interval between index tumor presentation and diagnosis of MPCs was eight months to twelve years. MPCs occurred in seventy percent index oral cavity squamous cancers, which were located in head and neck regions, and in sixty-two percent index hypopharynx cancers and seventy-nine percent index laryngeal cancers, which were located in remote organs. The incidence of MPCs in esophagus and lung was higher than that in other remote organs. Among the various MPCs in this serials, the incidence of the disease appeared to be the highest in esophagus, accounting for twenty-four percent of all cases. The total three- and five-year survival rates were 32.4% and 22.5%, respectively. Of all MPCs patients, the three-year survival rate for patients who received different therapies for their MPCs was obviously higher than that of untreated patients (P < 0.01, Chi-square test). CONCLUSIONS: Esophageal carcinoma is the most common second primary cancer among the various MPCs of the head and neck squamous carcinomas. Oral cavity cancers tend to have more MPCs in the head and neck regions, and laryngeal and hypopharyngeal cancers are easily to be associated with MPCs in the remote organs. Regular follow-up and early diagnosis with effective treatment can help to improve the survival of MPC patients in head and neck squamous cell carcinomas.

Adult↗

[The expressions of Ki67 and VEGF in squamous cell carcinoma of larynx and the correlation between the two marks].

OBJECTIVE: To investigate the expression of Ki67 and VEGF in squamous cell carcinoma of larynx and the correlation between Ki67 and VEGF. METHOD: The expression of Ki67 and VEGF in squamous cell carcinoma of larynx tissues of 40 cases were studied by immunohistochemical staining. RESULT: The expression of Ki67 and VEGF in squamous cell carcinoma of larynx tissues were higher than those in mucosa of laryngeal cavity (P<0.01). The expression of the two marks in squamous cell carcinoma of larynx with the metastasis of lymph nodes were higher than those without metastasis (Ki67: P<0.05, VEGF: P<0.01). Age and sex did not change the expression obviously (P>0.05). There was a positive correlation between T-stage and immunohistochemical staining (P<0.05). There was also a positive correlation in staining intensity between Ki67 and VEGF (r = 0.823, P<0.01). CONCLUSION: Ki67 and VEGF are objective marks to estimate the behaviors of squamous cell carcinoma of larynx, and they can do help to the diagnosis, the judgment of stages and the treatment of carcinoma of larynx.

Aged↗

[Relation between vascular endothelial growth factor expression and clinical pathological character in laryngeal squamous cell carcinoma].

OBJECTIVE: To approach the relation between vascular endothelial growth factor (VEGF) expression and clinical pathological character in laryngeal squamous cell carcinoma. METHOD: Immunohistochemical staining (SP) was used to evaluated the expression of VEGF and microvessel count (MVC) in tumor tissues from 87 patients with laryngeal squamous cell carcinoma. RESULT: VEGF immune response was mainly localized to the tumor cell cytoplasm, positive rate was 77%. In laryngeal squamous cell carcinoma, the wider the tumor invaded, the stronger VEGF expressed, the fewer the tumor invaded, the weaker VEGF expressed (P < 0.05); The lower the tumor differentiated, the stronger VEGF expressed, the higher the tumor differentiated, the weaker VEGF expressed (P < 0.05); The stronger VEGF expressed, the more MVC were (P < 0.01); The mean MVC in tumor tissues was obviously higher than that in surgical margin tissues (P < 0.01). CONCLUSION: In laryngeal squamous cell carcinoma, the expression of VEGF was markedly correlated with tumor stage and differentiation, was positively correlated with MVC. As a result, VEGF may have an important role in the progression of laryngeal squamous the carcinoma.

Adult↗

[Effectiveness of chemoradiotherapy for three cases of squamous cell anal carcinoma].

We report three patients with squamous cell anal carcinoma who were treated by chemoradiotherapy. Case 1: A 62-year-old female with squamous cell anal carcinoma invading the vagina underwent a posterior pelvic exenteration. She had paraaortic lymph node metastases. She was treated by chemoradiotherapy with 5-FU/CDDP and external irradiation (50 Gy) as an adjuvant therapy, and survived for 5 years. Case 2: A 74-year-old female with anal squamous cell carcinoma Stage II was treated by chemoradiotherapy with tegafur/uracil, external irradiation (30 Gy) and interstitial irradiation (24 Gy). She is currently living without any signs of recurrence for 3 years and 8 months. Case 3: A 53-year-old female with anal squamous cell carcinoma Stage IIIa was treated by chemoradiotherapy using 5'-DFUR and external irradiation (66 Gy). She is currently living without any signs of recurrence for 1 year and 9 months. The prognosis of anal squamous cell carcinoma that received Cur B or C resection was extremely poor with a median survival time (MST) of 7 or 6 months. Chemoradiotherapy seems to be effective as the first line treatment.

Aged↗

[Hypermethylation of the death-associated protein kinase promoter in laryngeal squamous cell cancer].

OBJECTIVE: To explore the relationship between hypermethylation of the promoter of death-associated protein kinase (DAPK) gene and laryngeal squamous cell cancer. METHODS: Promoter hypermethylation and mRNA expression of DAPK gene were detected by methylation-specific PCR, RT-PCR and gene sequencing. RESULTS: Among the 58 patients with laryngeal squamous cell cancer, hypermethylation of DAPK promoter was detected in 39 cases (67.2%). There was no significant difference in hypermethylation in relation to pathological grade and clinical staging, but a highly significant difference was observed between patients with and without lymph node metastasis (N0 and N1) (P < 0.001). DAPK promoter hypermethylation was detected in tumor adjacent tissues in 6 of the 58 cases. DAPK mRNA was not expressed in all laryngeal squamous cell cancers having hypermethylation of DAPK promoter, whereas it was expressed in normal laryngeal mucosa, laryngeal squamous cell cancers without hypermethylation and tumor adjacent tissues. CONCLUSION: Hypermethylation of DAPK promoter is associated with loss of its transcription in laryngeal squamous cell carcinoma. The high frequency hypermethylation of DAPK promoter illustrates its potential clinical application as tumor marker for diagnosis and prognosis.

Adult↗