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PubMed1992

The utility of squamous cell carcinoma antigen for the follow-up of patients with squamous cell carcinoma of the anal canal.

BACKGROUND: Thirty-three patients with histologic documentation of squamous cell carcinoma (SCC) of the anal canal underwent prospective serial collection of 234 serum samples for radioimmunoassay of SCC tumor-associated antigen. METHODS: There were 23 female and 10 male patients, with a median age of 55 years. Twenty-two of the 33 patients had multimodality therapy with radiation therapy and chemotherapy as initial treatment. RESULTS: The median follow-up was 22 months (range, 4-52 months), with a median of 13 serum specimens per patient (range, 1-23 specimens). Twenty-eight patients currently have no evidence of disease, 4 patients are alive with disease, and 1 patient died with disease. CONCLUSION: In these 33 patients, the sensitivity of the SCC tumor-associated antigen was 76%, specificity 86%, and positive predictive value 62%.

Adult↗

PubMed1994

The multicentric occurrence of squamous epithelial dysplasia and squamous cell carcinoma in the esophagus.

BACKGROUND: The biologic significance of esophageal dysplasia has not yet been completely elucidated, especially regarding the process of multiple occurrences of squamous cell carcinoma. METHODS: The multiplicity of dysplasia in 73 patients with solitary carcinoma of the esophagus (Group I) and 21 with multiple carcinomas (Group II) was compared in surgically resected specimens. RESULTS: Thirty-nine second carcinomas were identified in 13 patients of Group II, and all were superficial. The incidences of five or more isolated dysplasias in cases without continuity to a carcinomatous lesion, was 6.8% and 66.7% in Groups I and II, respectively (P < 0.01). In a case with three or more carcinomas, the incidence increased to 84.6%. The coexistence of all grades of isolated dysplasias was observed in 10 patients (47.6%) in Group II but in only 6 patients (8.2%) in Group I (P < 0.01). CONCLUSIONS: These findings suggest that various degrees of evolving biologically related lesions, such as dysplasia and carcinoma, can occur multicentrically in the same esophagus.

Carcinoma in Situ↗

PubMed2006

Effect of Bethesda 2001 on reporting of atypical squamous cells (ASC) with special emphasis on atypical squamous cells-cannot rule out high grade (ASC-H).

We compared the overall ASC rate and the outcomes for women with different categories of ASC before and after TBS 2001 to evaluate the impact of TBS 2001. Our laboratory reported ASC in four subcategories before TBS 2001; ASC, favor reactive (ASC-R), favor low-grade squamous intraepithelial lesion (SIL) (ASC-L), undetermined significance (ASC-US), and ASC-H. Since the implementation of TBS 2001, we have been reporting ASC as ASC-US and ASC-H. After TBS 2001, our ASC rate decreased from 6.2% to 4% (P < 0.0001). Before TBS 2001, ASC-R carried the same risk as ASC-US for underlying condyloma/CIN 1. Moreover, ASC-R was rarely associated with CIN 2 or 3. Before TBS 2001, ASC-H captured more low-grade (condyloma/CIN 1) and less high-grade (CIN 2, 3, and SCC) lesions compared to after TBS 2001. More women with ASC-H after TBS 2001 underwent colposcopy (80% vs. 71%, P < 0.05). Twenty-two percent of women with ASC-H required 2-4 colposcopies to identify the high-grade lesion. Our results confirm that consistent application of TBS 2001 terminology for ASC reduces the ASC rate, and better identifies women at high risk for CIN 2, 3, and SCC. In addition, ASC-H requires very close clinical follow-up as a significant percentage of women require more than one colposcopy to identify the high-grade lesion.

Colposcopy↗

PubMed1990

Establishment of an esophageal squamous cell carcinoma tumor line and development of serum squamous cell carcinoma-related antigen in athymic nude mice.

A serially transplantable tumor line (IMEs-1) derived from human esophageal squamous cell carcinoma (SCC) of a 71-year-old female was established in nude mice. The histology of IMEs-1 closely resembled that of the original tumor and tumor doubling time was 3.2 days. Production of SCC-related antigen (SCCRA) and carcinoembryonic antigen (CEA) in the serum of tumor-bearing mice was observed. To evaluate the usefulness of SCCRA for esophageal cancer, the relationship between the serum levels of SCCRA and tumor burden in athymic nude mice bearing IMEs-1 was studied. The mean serum levels of SCCRA, as determined by radioimmunoassay, gradually rose in direct proportion to the tumor growth gauged by tumor volume. However, the serum levels of CEA did not increase until the last few weeks of the assay. These results suggest the possibility of using SCCRA as a tumor marker for esophageal SCC. In addition, this nude mouse assay system will provide a theoretical model to study the usefulness of SCCRA.

Aged↗

PubMed1992

Serum squamous cell carcinoma antigen levels in invasive squamous vulvar cancer.

Squamous cell carcinoma (SCC) antigen levels were studied in 34 patients with primary (N = 27) or recurrent (N = 7) SCC of the vulva. In primary disease, the SCC antigen level was greater than 2.5 ng/ml in only four patients (15%). Elevated antigen levels ranged from 2.7-18.0 ng/ml. All of these patients had advanced disease by either clinical or surgical staging systems. Four of twelve patients with inguinal metastasis had elevated SCC antigen levels. In two of these patients the inguinal nodes were abnormal to palpation. No association of the SCC level and the degree of tumor differentiation was observed. SCC antigen levels were increased slightly (2.7-4.5 ng/ml) in three of six patients with locally recurrent disease. In one patient with distant recurrence the SCC antigen was 15.3 ng/ml. In both primary and recurrent disease all elevated SCC antigen levels decreased with effective therapy. Vulvar cancer is primarily a local disease that is easily assessed by physical examination. An effective tumor marker in vulvar cancer would benefit only the rare patient with distant but not local disease.

Antigens, Neoplasm↗

PubMed2000

Tissue polypeptide specific antigen and squamous cell carcinoma antigen for early prediction of recurrence in lung squamous cell carcinoma.

One of the major problems in the follow-up of patients with lung cancer is the early detection of recurrent disease. Tumor markers have been found helpful in detecting early recurrent disease. The aims of this study were to evaluate and compare the clinical usefulness of serial and simultaneous measurement of tissue polypeptide antigen (TPS) and squamous cell carcinoma (SCC) antigen for the early prediction of recurrence in patients with SCC of the lung. Sixty patients with SCC of the lung, including 25 patients with recurrence and 35 patients without recurrence after 1 year's follow-up after surgery, were enrolled in this study. The serial serum levels of TPS and SCC antigen were measured before surgery and 1 week, 1 month, 3 months, 6 months, 9 months, and 12 months after the operation for early detection of recurrence. The results revealed that (1) the mean serum values of TPS were significantly greater at all times after surgery in the 25 patients with recurrent SCC compared with the 35 patients without recurrent SCC, and (2) the mean serum values of SCC antigen were significantly greater only at 9 and 12 months after surgery in the 25 patients with recurrent SCC compared with the 35 patients without recurrent SCC. We conclude that TPS is a better marker than SCC antigen for early prediction of SCC recurrence in the lung.

Adult↗

PubMed1993

Squamous epithelial dysplasia associated with squamous cell carcinoma of the esophagus.

To investigate the relationship between dysplasia and carcinoma of the esophagus, 159 cases of esophageal carcinoma without any preoperative treatment were reviewed retrospectively. There were 75 dysplastic lesions in 32 cases (20.1%). The incidence of co-existence of dysplastic lesions was 0, 58.3, 31.3, 20.8 and 11.4% in intra-epithelial, mucosal and submucosal cancers and those invading the proper muscular layer and adventitia, respectively. Thus, excluding the cases of intra-epithelial carcinoma, the less advanced the lesion, the higher the incidence of dysplasia. Epithelial dysplastic lesions were classified as 12 with mild, 33 with moderate and 30 with severe degrees of dysplasia. Although the continuity of dysplastic lesions to the areas of carcinoma was not so frequent (48.0%), it was more often encountered in severe dysplasia rather than in moderate or mild dysplasia, which suggested some relationship between the severity of dysplasia and carcinoma. In the cases with a dysplastic lesion the multiplicity of squamous cell carcinoma and the intra-epithelial spread of the main lesion were more frequently seen (P < 0.001), suggesting a multicentric occurrence of dysplastic lesions and carcinomas.

Carcinoma, Squamous Cell↗

PubMed2005

Pretreatment levels of serum squamous cell carcinoma antigen and urine polyamines in women with squamous cell carcinoma of the cervix.

OBJECTIVES: To investigate whether pretreatment levels of serum squamous cell carcinoma antigen (SCCA) and urine polyamines can predict lymph node metastases in patients with early stage cervical carcinoma. METHODS: Pretreatment measurement of serum SCCA and urine polyamine levels was carried out for 419 women. Of those women, 104 with stage IB and IIA cancer received radical surgery and had tumor size reassessed postoperatively. RESULTS: The women had increased levels of serum SCCA (>2.0 ng/mL) and elevated urine polyamines (>45 micromol/g of creatinine) with advanced cancer stage (P<0.01). The median SCCA level was significantly higher in women with metastatic disease than that in those without lymph node involvement (3.9 vs. 1.1; P<0.01). Women with nodal involvement also had significantly higher median levels of urine polyamines than those without nodal disease. CONCLUSIONS: Pretreatment measurement of SCCA and urine polyamine levels may help in predicting lymph node metastases in women with early stage cervical carcinoma.

Adult↗

PubMed1998

A subcloned human esophageal squamous cell carcinoma cell line with low thrombomodulin expression showed increased invasiveness compared with a high thrombomodulin-expressing clone--thrombomodulin as a possible candidate for an adhesion molecule of squamous cell carcinoma.

Thrombomodulin (TM) is an endothelial cell surface glycoprotein which converts thrombin from a procoagulant protease to an anticoagulant. We have previously reported that TM is a useful marker for immunohistochemical diagnosis of angiogenic tumors and also have reported that TM is expressed on squamous cell carcinoma (SCC) of the human esophagus. In addition, the expression of TM is significantly decreased in metastatic foci in lymph nodes compared with that in primary lesions. In order to reveal the biological significance of TM in SCC, we subcloned and established two different cell lines, i.e. TM-high-expressing (TE3HTM) cells and TM-low-expressing (TE3LTM) cells, from a human SCC cell line, TE3, using fluorescence-activated cell sorter (FACS) and examined the biological characteristics of these variant cell lines. These tumor cells revealed very similar morphological figures in ordinary cultured conditions and showed almost equal growth rates under various cultured conditions. By the invasion assay of these tumor cells using matrigel, we found that TE3LTM cells showed significantly increased invasive ability compared with that of TE3HTM cells. Characteristic intercellular localization of TM and a different manner of invasiveness between TE3LTM cells and TE3HTM cells suggest that TM may act as a cell-to-cell interaction molecule.

Carcinoma, Squamous Cell↗

PubMed2002

Defining the glycophenotype of squamous epithelia using plant and mammalian lectins. Differentiation-dependent expression of alpha2,6- and alpha2,3-linked N-acetylneuraminic acid in squamous epithelia and carcinomas, and its differential effect on binding of the endogenous lectins galectins-1 and -3.

A thorough characterization of the properties of squamous epithelial cells is necessary in order to improve our understanding of the functional aspects of normal development and malignant aberrations. Up to now, studies have focused almost exclusively on monitoring distinct protein markers. With our growing awareness of the coding function of glycan chains of cellular glycoconjugates and their interaction with receptors (lectins) in situ, defining the glycophenotype of these cells has become an important issue. Whereas the commonly applied plant lectins are tools used to map the presence and localization of biochemically defined saccharide epitopes, the introduction of endogenous (mammalian) lectins to this analysis enables us to take the step from monitoring the presence of glycan to understanding the functional implications by revealing ligand properties of the detected epitope for tissue lectin. Thus, in this study we investigated a distinct aspect of glycosylation using plant and mammalian lectins, i.e. the linkage type of sialylation. We first mapped the expression profile of the type of sialylation (alpha2,3- or alpha2,6-linked) by plant lectins. Based on the hypothesis that this factor regulates accessibility of ligands for endogenous lectins we introduced two labeled galectins to this study. Galectin-3 (but not galectin-1) binding was related to cell differentiation in normal adult and developing epithelia, cultured epidermal cells, and carcinomas derived from these epithelia. The presented data suggest that alpha2,6-linked N-acetyl-D-neuraminic acid moieties could serve to mask galectin-3-reactive glycoepitopes. As a consequence, monitoring of the linkage type of sialic acid in glycans by plant lectins therefore has implications for the extent of glycan reactivity with endogenous lectins, pointing to a potential function of changes in sialylation type beyond these cell and lectin systems.

Animals↗

PubMed1998

Immunohistochemical staining for desmogleins 1 and 2 in keratinocytic neoplasms with squamous phenotype: actinic keratosis, keratoacanthoma and squamous cell carcinoma of the skin.

Desmosomes are intercellular junctions that have been shown to be down-regulated in certain types of carcinoma and that may play a role in suppression of invasion and metastasis. This paper describes an immunohistochemical study of three types of epidermal neoplasms with monoclonal antibody to desmoglein in order to determine how desmosomal staining correlates with the clinical, biological and histopathological features of these neoplasms. Actinic keratosis (AK) is the most common keratinocytic premalignant neoplasm that was reported to have a 10-20% rate of malignant transformation into squamous cell carcinoma (SCC). Keratoacanthoma (KA) is a benign neoplasm that involutes spontaneously after a few months of rapid growth. SCC is a malignant tumour capable of metastasis. Electron microscope studies of KA and SCC showed significantly reduced staining for desmosomes in SCC but not in KA. We have examined staining for desmoglein using the monoclonal antibody 33-3D, a mouse IgM monoclonal antibody, that recognizes the cytoplasmic domains of desmoglein (Dsg)1 and Dsg2 on frozen sections. Immunohistochemical staining of normal skin with this antibody revealed strong pericellular localization of the antigen, outlining the cell membranes of the keratinocytes. A series of 30 AKs, 12 KAs and 24 SCCs was stained immunohistochemically with 33-3D monoclonal antibody. All examined KAs showed extensive pericellular staining for Dsg. By contrast, juxtanuclear staining for Dsg was noted in 12 SCCs, and completely negative staining in seven SCCs. The five remaining SCCs showed focal pericellular staining for the Dsg marker. The most common finding in AK was focal pericellular staining for Dsg, with complete absence of staining in dysplastic areas (25 cases). In five cases negative pericellular staining in dysplastic areas was associated with juxtanuclear accumulation of the Dsg marker. A strong negative correlation between Dsg staining and degree of dysplasia was obtained. The Dsg pattern in KA is similar to normal epidermis and shows a clear difference between KA and SCC. AK has a limited loss of Dsg expression in a SCC-like pattern that is congruent with its premalignant nature. As the stain works on frozen tissue, it may be helpful for rapid differentiation in selected cases in cutaneous oncology and Mohs micrographic surgery. This antibody may also have great potential for the detection of the effects of chemopreventive agents in skin cancer.

Animals↗

PubMed2005

Immunity to squamous carcinoma in mice immunized with dendritic cells transfected with genomic DNA from squamous carcinoma cells.

Immunotherapy of squamous cell carcinoma (SCC) at an early stage of the disease increases the likelihood of success. We report a new vaccination strategy designed to prepare SCC vaccines from microgram amounts of tumor tissue, enabling the treatment of patients with minimal residual disease. The vaccine was prepared by transfer of sheared genomic DNA-fragments (25 kb) from KLN205 cells, an SCC cell line of DBA/2 mouse origin, into syngeneic bone marrow-derived mature dendritic cells (DCs). More than 90% of the transfected DCs took up DNA from the neoplasm and transferred genes were expressed as protein. The DCs expressed CD11c, CD11b, and the costimulatory molecules CD40, CD80 and CD86, characteristic of mature DCs. Syngeneic DBA/2J mice, highly susceptible to the growth of KLN205 cells, were injected intravenously (i.v.) with the transfected DCs, followed by a subcutaneous (s.c.) injection of the tumor cells. The strong immunogenic properties of the transfected cells were indicated by the finding that the survival of the tumor-bearing mice was prolonged (P<.001), relative to that of mice in various control groups. Enzyme-linked immuno spot (ELISPOT IFN-gamma) assays revealed the activation of cell-mediated immunity directed toward the SCC in mice immunized with the transfected DCs. Two independent in vitro cytotoxicity assays indicated the presence of robust cell-mediated immunity directed toward the SCC in mice immunized with the transfected cells.

Animals↗

PubMed1996

7,12-dimethylbenz[a]anthracene-induced 'early' squamous cell carcinoma in the Golden Syrian hamster: evaluation of an animal model and comparison with 'early' forms of human squamous cell carcinoma in the upper aero-digestive tract.

To test and optimize photodynamic therapy of early cancers in the upper aero-digestive tract and oesophagus, we sought an appropriate animal model, which was found in the 7,12-dimethylbenz[a]anthracene-induced early squamous cell carcinoma in the Golden Syrian hamster. This chemically induced neoplasm is shown, by histology and immunohistochemistry, to pass through similar stages of early cancer development as its human counterpart. Its time sequence is highly reproducible, leading to a well differentiated carcinoma in situ and microinvasive carcinoma in the hamster cheek pouch over a period of 10 weeks.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed2003

Squamous cell carcinoma antigen: a role in the early identification of nodal metastases in men with squamous cell carcinoma of the penis.

OBJECTIVE: To evaluate whether serum squamous cell carcinoma antigen (SCCAg) measurements may be of use in identifying nodal metastases in patients with SCC of the penis after treating the primary tumour. PATIENTS AND METHODS: The levels of SCCAg were analysed in 11 men with penile SCC between 1994 and 2001. RESULTS: An elevated SCCAg level had a sensitivity of 57% (95% confidence interval, CI, 18-90%) and a specificity of 100% (CI 40-100%) for nodal metastases. Levels of SCCAg increased exponentially in patients who developed nodal metastases after treatment of the primary tumour, and were elevated before clinical or radiological evidence of nodal disease. CONCLUSION: Either the absolute level or the rate of rise of SCCAg may be a useful tool with which to follow patients after excision of the primary tumour. It may be more sensitive than computed tomography and magnetic resonance imaging in detecting recurrence, but further evaluation is needed.

Antigens, Neoplasm↗

PubMed1998

[The SCC antigen is not a reliable tumor marker in the ENT area. Value of squamous cell carcinoma antigen in diagnosis and follow-up of squamous epithelial carcinoma in the head-neck area. Results of a retrospective study over 6 years].

BACKGROUND: In the early 1970s, progress in chemical analysis allowed the assessment of low concentration substances in blood and other body fluids. These techniques led to development of hitherto unknown diagnostic facilities which were tested with respect to malignant tumors. In those days SCC-A was considered a promising substance for aiding in diagnosis and observation in patients with SCC. METHODS: This retrospective study investigates the correlation between tumor size and tumor progress and the SCC-A level in a group of 322 patients (male: n = 291, age 24-87 yrs, mean 56 yrs: female: n = 31, age 38-82 yrs, mean 70 yrs). RESULTS: The diagnostic value of SCC-A turned out to be poor. In 78%, SCC-A levels were low and neither correlated with tumor size nor the presence of metastases. In follow-up the situation was even worse: A reliable correlation between SCC-A and the course of disease was found in 5.8% of patients only. CONCLUSION: The SCC-A could neither reliably contribute to diagnosis nor to follow-up of patients with squamous cell carcinomas of the head and neck.

Adult↗

PubMed2003

Prediction of survival with squamous cell carcinoma antigen in patients with resectable esophageal squamous cell carcinoma.

BACKGROUND: Increased preoperative serum squamous cell carcinoma antigen (SCC-Ag) concentrations have been found to be associated with advanced stage and poor prognosis in lung and cervical cancers. Because little was known about the significance of SCC-Ag concentration in patients with esophageal cancer, the aim of this study was to analyze the clinicopathologic significance of SCC-Ag in patients with esophageal SCC. PATIENTS AND METHODS. Preoperative SCC-Ag concentration was measured with enzyme-linked immunosorbent assay in 309 patients with primary esophageal SCC. All patients underwent curative radical surgery without any preoperative therapy. In 215 of 309 patients, carcinoembryonic antigen (CEA) was also measured to compare clinical significance of CEA with that of SCC-Ag. The prognostic significance for survival of SCC-Ag concentrations was studied with multivariate analysis with Cox proportional hazards model. RESULTS: The SCC-Ag concentration and the positivity rate of SCC-Ag were significantly elevated in patients associated with tumor progression. Statistically significant differences in SCC-Ag concentrations and SCC-Ag positivity rates were observed depending on tumor size, tumor depth, lymph node status, and distant metastasis. Although CEA was not a prognostic factor (P =.21), a high SCC-Ag concentration was a significant prognostic factor (P <.01). Multivariate analyses indicated that T factor had the best predictive power, but SCC-Ag concentration contained additional, independent prognostic information. CONCLUSION: Our findings suggest that preoperative serum SCC-Ag concentrations might provide a predictive information for tumor progression and survival in patients with esophageal SCC.

Adult↗

PubMed1997

Early diagnosis of mucosal squamous cell carcinoma of the esophagus: including two interesting cases of superficial spreading-type and multicentric-type squamous cell carcinomas.

We reviewed 10 patients with esophageal mucosal carcinoma in order to improve the early diagnosis of the disease. Histologically seven of the 14 lesions were carcinomas in situ (epithelial cancer), and the other seven lesions were carcinomas confined to the mucosa other than epithelial cancer (muscularis mucosae cancer), all 14 lesions were squamous cell carcinomas (SCC). One of these seven mucosal SCC, which demonstrated an extensive spreading-type SCC in which the size of the SCC was 7 cm long while extending entirely around the esophageal lumen in circumferential spread, is described in detail, and multiple epithelial cancers existed separately in one case. Eleven lesions diagnosed before operation showed abnormal findings on conventional endoscopy regardless of the size and depth of transmural invasion. An additional lesion was visible with dye endoscopy as an unstained area, but it was not visible with radiography or conventional endoscopy. Dye endoscopy using Lugol solution is very important because it allows detection and evaluation of the extent of esophageal mucosal cancer.

Aged↗

PubMed2000

Cytokeratin fragment 19 and squamous cell carcinoma antigen for early prediction of recurrence of squamous cell lung carcinoma.

Sixty patients with squamous cell carcinoma (SCC) of the lung, including 25 cases with recurrence and 35 cases without recurrence 1 year after operation, were enrolled in this study. The serial serum levels of cytokeratin fragment 19 (CYFRA 21-1) and SCC antigen were measured before operation and 1 week, 1 month, 3 months, 6 months, 9 months, and 12 months after operation for early detection of recurrence. The results revealed that 1) mean serum values of CYFRA 21-1 were significantly higher at early and any times after operation in 25 patients with recurrent SCC when compared with 35 patients without recurrent SCC; and 2) mean serum values of SCC antigen were significantly higher until 9 and 12 months after operation, in 25 patients with recurrent SCC when compared with 35 patients without recurrent SCC. We conclude that CYFRA 21-1 is a better marker than SCC antigen for early prediction of SCC recurrence in the lung.

Aged↗