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PubMed1975

Differentiation of squamous carcinoma of the larynx as a determinant of prognosis.

The changes seen by light and electron microscopy in the differentiation of squamous carcinoma are described. The grading of the differentiation of squamous carcinomas by overall impression and by quantitative methods are discussed. Reasons are given for retaining the former in the assessment of prognosis. Other differentiating phenomena, particularly retention of basement membrane in the formation of rounded rather than jagged growing edges, are discussed. The differentiating effect of radiation on squamous carcinomas is discussed as a means of assessing the efficacy of the radiation. A similar differentiating effect of bleomycin, a cytotoxic drug, on human squamous carcinoma is described. Using electron microscopical criteria belomycin also increases differentiation of a transplanted, experimental, poorly differentiated squamous carcinoma and human laryngeal carcinoma cells in tissue culture. The significance and possible practical utilization of this phenomenon are discussed.

Bleomycin↗

PubMed1984

Skin calcium-binding protein in squamous metaplasia of human uterine cervix.

The distribution of skin calcium-binding protein in squamous cell metaplasia of human endocervix, in normal human skin, and in ovarian cancer was determined by the immunofluorescence technique. A rabbit antiserum specific to rat SCaBP was characterized by Ouchterlony immunodiffusion and by immunoprecipitation of 125I-labeled SCaBP. The specificity of antibody labeling was demonstrated by using preimmune rabbit serum and SCaBP antiserum competitively absorbed with purified SCaBP. In normal human skin SCaBP was found exclusively in the basal layer cell cytoplasm. This protein was not detected in normal columnar epithelium of endocervix. Epithelial tissues in the zone of transition between the cylindrical epithelium of the endocervical mucosa and the stratified squamous epithelium of the exocervix were obtained from 14 patients with a wide variety of squamous cell metaplasia. In the early stage of metaplasia SCaBP was detected exclusively in the cytoplasm of reserve undifferentiated cells. In the terminal stage of metaplasia the SCaBP was present only in the basal cell layer. SCaBP was found in several layers of dysplastic tissue, and this distribution appeared to be related to the loss of normal maturation of the epithelium. SCaBP was also present in squamous cell carcinoma of endocervix especially in the least differentiated regions of the tumor. No SCaBP was detected in any ovarian cancer cells. These findings are potentially useful as a means of early detection of squamous metaplasia and of distinguishing premalignant anaplastic lesions from those that are benign and nonproliferative. In addition, the presence of SCaBP in tumors derived from metaplastic epithelia and its absence in the ovarian cancer indicate that immunohistochemical search for this protein might be of value in tumors in which an epidermoid origin is a possibility.

Animals↗

PubMed1984

Invading squamous cell carcinoma can retain a basal lamina. An immunohistochemical study using a monoclonal antibody to type IV collagen.

A monoclonal antibody to human glomerular type IV collagen has been characterized and used in an immunohistochemical study of the distribution of this basement membrane protein in dysplasias, intraepithelial carcinomas, and infiltrating squamous cell carcinomas. Four squamous carcinoma cell lines established as xenografts in nude mice were also examined. In normal epidermis and mucosae, the basement membrane was clearly defined and intact. In areas of intraepidermal carcinoma, the basal lamina as defined by the antibody was usually continuous, and defects were only present in areas associated with an inflammatory infiltrate. Invasive squamous cell carcinomas, regardless of the degree of differentiation had a clearly delineated basement membrane at the epithelial stromal interphase. In areas of invasion, far removed from the in situ component, there were protrusions of tumor cells through the basement membrane into the stroma. Other abnormalities of basement membrane production such as aggregation of basement membrane and reduplication of the basal lamina were also associated with the carcinomas. There was a similar distribution of basal lamina material in involved lymph nodes and in squamous cell carcinomas that were growing as xenografts in nude mice. Our studies suggest that the loss of basement membrane type IV collagen is not generally associated with invasive squamous cell carcinomas and is not likely to be useful in the assessment of early invasion in this tumor. The similar distribution of type IV collagen in the xenografts and in the infiltrating tumors suggests that this system, in conjunction with the use of the same cell lines in vitro, will provide a model with which to study the control of deposition of type IV collagen.

Antibodies, Monoclonal↗

PubMed1984

Heterogeneity of a tumor antigen TA-4 of squamous cell carcinoma in relation to its appearance in the circulation.

The heterogeneity of a tumor antigen TA-4 of squamous cell carcinoma was studied by using isoelectric focusing (IEF). IEF of squamous cell carcinoma tissue of the uterine cervix showed 2 major peaks of TA-4 with pI values of 5.9 to 6.2 (acidic TA-4) and 6.3 to 6.6 (neutral TA-4). The non-malignant squamous epithelium of the uterine cervix showed a major TA-4 peak at pI 6.3 to 6.6 (neutral TA-4), while TA-4 in the blood of patients with squamous cell carcinoma was mainly eluted at pI 5.9 to 6.2 (acidic TA-4). These results indicated that acidic TA-4 is implicated in the appearance of this antigen in the circulation of patients with squamous cell carcinoma.

Antigens, Neoplasm↗

PubMed1981

Squamous cell carcinoma of gallbladder--report of two cases and review of literature.

Two cases of a well-differentiated keratinizing squamous cell carcinoma of the gallbladder were reported. Pathologic analysis of this rare neoplasm was made in conjunction with cases of the gallbladder carcinoma of a squamous cell variety reported in literatures. The squamous cell carcinoma is characterized by a well-localized growth and a rarity or lack of metastasis. These characteristics make a good contract with an adenosquamous carcinoma of the gallbladder which usually infiltrates rather extensively and metastasizes widely. Thus the adenosquamous carcinoma should be sequestered from group of squamous cell carcinoma. Radical operative procedures may well be encouraged on selected cases of squamous cell carcinoma.

Adenocarcinoma↗

PubMed1993

[Primary squamous cell carcinomas of the endometrium. Clinico-pathologic data and histogenetic classification].

Primary squamous cell carcinomas of the endometrium are rare tumours. We have studied 7 primary and 2 secondary squamous cell carcinomas immunohistochemically with anti-all-cytokeratin (KL 1), anti-CEA and anti-vimentin. The non-keratinizing carcinomas and the non-keratinizing component of the keratinizing carcinomas showed a strong expression of vimentin. Contrary to this, the keratinizing parts were strongly positive with anti-CEA. Additionally, some cases showed a direct transformation of the (dysplastic) glandular endometrial epithelium into neoplastic squamous cells. These findings suggest that the primary squamous cell carcinoma of the endometrium is the result of a bidirectional differentiation of pluripotent endometrial precursor cells. Like in other non-endometrioid adenocarcinomas, such metaplasias develop from pluripotent Müllerian epithelium. They show various differentiations, perhaps endocervical determination with keratinization and positive reaction against CEA or primitive endometrioid with squamous cell appearance, positive anti-vimentin reaction and non-keratinization.

Adult↗

PubMed1995

[Description of a case of squamous cell carcinoma of the renal pelvis].

A case of squamous cell carcinoma of renal pelvis is reported. A 73-year-old Caucasian male complained of macrohematuria. The echography and Computer Tomography scan of the abdomen and pelvis revealed a large tumor mass in the right kidney associated with lymphadenopathy. A nephrectomy of the right kidney and lymphadenectomy were performed. The isotologic examination revealed a squamous carcinoma of the renal pelvis involving the renal parenchyma and extending to the perirenal fat. The regional lymph nodes were also involved. Neoplastic invasion of inferior vena cava was found. Squamous carcinoma in situ and squamous metaplasia were noted in the urothelium adjacent to the tumor. Three months later an echography revealed a local recurrence of the disease. The patient underwent adjuvant chemotherapy. The aggressive course of the disease is in agreement with the poor prognosis of squamous carcinomas of the renal pelvis as previously reported in the literature.

Aged↗

PubMed1995

[Assessment of nucleolar organizer regions (Ag-NORs) in bronchial dysplasia and roentgenographically occult bronchogenic squamous cell carcinoma].

Mean argyrophil nucleolar organizer regions (Ag-NORs) per nucleus were determined on columnar epithelium, bronchial dysplasia, roentgenographically occult squamous cell carcinoma and squamous cell carcinoma with roentgenographically findings in 76 formalin-fixed, paraffin-embedded resected specimens. 1) Mean Ag-NOR counts per nucleus (mean +/- standard deviation) were 1.67 +/- 0.30 in 10 columnar epitheliums, 2.74 +/- 0.41 in 13 lesions with bronchial dysplasia, 3.75 +/- 0.59 in 57 lesions with roentgenographically occult squamous cell carcinoma and 4.44 +/- 0.51 in 14 lesions with squamous cell carcinoma with roentgenographically findings. There were significant differences between each two groups. 2) In lesions with squamous call carcinoma, mean Ag-NOR counts per nucleus of T2, T3 or T4 tumor were significantly higher than those of T1 tumor. Mean Ag-NOR counts per nucleus of N1 or N2 tumor were significantly higher than those of N0 tumor.

Aged↗

PubMed1993

Expression of keratins 1, 6, 15, 16, and 20 in normal cervical epithelium, squamous metaplasia, cervical intraepithelial neoplasia, and cervical carcinoma.

Expression of keratins 1, 6, 15, 16, and 20 was examined in normal cervical epithelia, squamous metaplasia, various grades of cervical intraepithelial neoplasia, and both squamous cell carcinomas and adenocarcinomas of the cervix with monospecific antibodies. Ectocervical epithelium contains all of these keratins except keratin 20. They show a heterogeneous distribution, with a basally restricted detection of keratin 15. Endocervical columnar cells were found to contain significant amounts of keratin 16, whereas the subcolumnar reserve cells expressed considerable amounts of keratin 15 and 16, and frequently keratin 6. These reserve cell keratins were also found in immature and mature squamous metaplastic epithelium. In the cervical intraepithelial neoplastic lesions they were generally found with increasing intensity as the severity of the lesion progressed. In the keratinizing variety of squamous cell carcinoma of the cervix, these three keratins seem to constitute an important part of the intermediate filament cytoskeleton, whereas in nonkeratinizing squamous cell carcinoma, they occur to a much lesser extent. Surprisingly, these keratins were also occasionally found in adenocarcinomas. From these data we conclude that the keratin phenotype of reserve cells and endocervical columnar cells is more complex than previously suggested. In particular, the keratins occurring in reserve cells are also present in most of the premalignant and in a considerable number of the malignant lesions of the cervix. The differentiation features of the various carcinoma types are, however, reflected in their specific keratin filament composition.

Adenocarcinoma↗

PubMed1995

Combined chemoradiotherapy for locally advanced squamous cell carcinoma of the bulbomembranous urethra: a case report.

Patients with locally advanced squamous cell carcinoma of the bulbomembranous urethra fare poorly whether they undergo surgery or primary radiotherapy. Combined chemoradiotherapy has been used with encouraging results in the treatment of squamous cell carcinoma of the anal canal and esophagus, and limited reports suggest that this management may show promise in the control of squamous cell carcinoma of the urethra. We report good results in a man with locally advanced squamous cell carcinoma of the bulbomembranous urethra who underwent concomitant radiotherapy, mitomycin C and 5-fluorouracil. We encourage the use of this regimen in patients with urethral squamous cell carcinoma as well as the reporting of results.

Antineoplastic Combined Chemotherapy Protocols↗

PubMedDate not supplied

Malignant squamous cell elements in the ovarian cancer: report of 5 cases and review of the literature.

Five cases of ovarian cancer are presented in which malignant squamous cell elements were present. Three of the cases were adenosquamous carcinoma without composite endometriosis, mature cystic teratoma or with mixed mesodermal tumor. The other two cases were squamous cell carcinoma which arose in mature cystic teratoma, one of them being in situ carcinoma. Among cases of adenosquamous carcinoma, one composed predominantly of squamous cell element and foci of endometrioid adenocarcinoma was found. In this case, transitional figures between the two components were found. In other cases of adenosquamous carcinoma, components of adeno- and squamous cell carcinoma were intermingled in each carcinoma cell nests. Thus a large variety of histogenesis and microscopic figures were seen in malignant squamous cell elements in the ovarian cancer.

Adult↗

PubMed1995

Squamous differentiation in small-cell carcinoma of the parotid gland.

Small-cell anaplastic carcinomas comprise 1% to 2% of major salivary gland malignant tumors and demonstrate an aggressive clinical course. The initial classification of salivary small-cell anaplastic carcinoma was based on the ultrastructural identification of membrane-bound dense core granules, confirming neuroendocrine differentiation. These neuroendocrine-type small-cell carcinomas were felt to arise from neuroendocrine stem cells that migrated to the salivary gland from the neural crest. Absent neuroendocrine differentiation by ultrastructural evaluation was felt to signify origin from ductal cells. Immunohistochemical study has revised this concept because many small-cell carcinomas express at least one neuroendocrine marker, even in the absence of ultrastructural evidence of neuroendocrine differentiation. In addition, glandular differentiation both by ultrastructural and light microscopic study has been found in cases showing neuroendocrine differentiation. Ultrastructural evidence for squamous differentiation, such as desmosomes and tonofilaments, has also been recognized. These new findings have led to a revision of the old histogenetic hypothesis. All of these small-cell carcinomas are presumed to arise from a hypothetical ductal stem cell that can undergo neuroendocrine, squamous, or glandular differentiation. We report a small-cell anaplastic carcinoma of the left parotid gland in a 61-year-old man with squamous differentiation identified by light microscopy and confirmed by immunohistochemical expression of predominantly high rather than low molecular weight cytokeratins. This tumor is distinctive because it shows an abrupt transition from small-cell anaplastic carcinoma with neuroendocrine differentiation to well-differentiated squamous differentiation, which was identified readily by light microscopy. Our findings support this new hypothesis of a single multipotential stem cell by demonstrating bidirectional neuroendocrine and squamous differentiation.

Carcinoma, Small Cell↗

PubMed1995

Induction of M(r) 92,000 type IV collagenase expression in a squamous cell carcinoma cell line by fibroblasts.

A previous investigation (Matsumoto et al., J. Oral Pathol. Med., 18: 498-501, 1989) has shown that the in vitro invasion of a collagen gel by squamous cell carcinoma can be substantially augmented in the presence of fibroblasts. Therefore, we undertook a study to determine if the production of collagenase(s) by a squamous cell carcinoma cell line, UM-SCC-1, was up-regulated by fibroblasts. Cocultivation of UM-SCC-1 cells with MDA-TU-138 fibroblasts, both established from the oral cavity, resulted in a dose-dependent increase in the activity of a M(r) 92,000 gelatinase as shown by zymography. Augmented M(r) 92,000 gelatinase activity was a consequence of the stimulation of the UM-SCC-1 cells by a soluble, fibroblast-derived factor since this effect could be reproduced with fibroblast-conditioned medium but not with glutaraldehyde-fixed fibroblasts. The increased M(r) 92,000 gelatinolytic activity could be accounted for by an increase in M(r) 92,000 type IV collagenase (MMP-9) protein, as demonstrated by Western blotting for this metalloproteinase. Trypsin treatment of the fibroblast-conditioned medium abolished its ability to increase MMP-9 secretion by UM-SCC-1 cells. Furthermore, fractionation of the fibroblast-conditioned medium revealed a M(r) 3,000-10,000 soluble factor(s) which was responsible for the augmented production of MMP-9 by UM-SCC-1 cells. To determine if the increased production of MMP-9, in response to the fibroblasts, was a consequence of increased promoter activity, UM-SCC-1 cells were transiently transfected with a chloramphenicol acetyltransferase reporter driven by the MMP-9 promoter and plated on plastic or on a monolayer of MDA-TU-138 fibroblasts. A 4-5-fold stimulation of MMP-9 promoter activity was observed with UM-SCC-1 cells plated with the MDA-TU-138 fibroblasts, when compared with similarly transfected cells recultured on plastic. In conclusion, we have demonstrated that MMP-9 expression in a squamous cell carcinoma cell line is augmented by a fibroblast-derived protein(s). This finding indicates a role for stromal cells in the regulation of MMP-9 expression in squamous cell carcinoma. The ability of fibroblasts to regulate MMP-9 expression in tumor cells in vitro may explain the observation that the amount of M(r) 92,000 type IV collagenase mRNA in tumor cells is highest at the tumor:stromal interface of resected squamous cell carcinoma.

Carcinoma, Squamous Cell↗

PubMed1994

Difference of allelotype between squamous cell carcinoma and adenocarcinoma of the lung.

We compared the frequency of loss of heterozygosity on all autosomal chromosomes among 41 squamous cell carcinomas and 119 adenocarcinomas, to analyze possible relationships of specific tumor suppressor gene(s) to each histological type. On the majority (28 of 36) of chromosomal arms tested, loss of heterozygosity was observed more frequently in squamous cell carcinomas than in adenocarcinomas; in nine of these locations (3p, 3q, 4q, 7p, 9q, 13q, 16q, 17p, and 21q), the frequency was statistically significant (3p, 3q, 4q, 9q, 13q, and 17p, P < 0.01; 7p, 16q, and 21q, P < 0.05, chi 2 test). In squamous cell carcinomas, the frequency of allelic loss on chromosome 9q (67%) fell between the frequencies of loss on chromosomes 3p (82%) or 17p (88%) and chromosome 13q (60%). On the other hand, in adenocarcinomas frequent loss of heterozygosity was observed on chromosomes 8q (32%), 9p (36%), 3p (40%), and 17p (51%). Furthermore, allelic losses on chromosomes 9p, 9q, and 13q tended to correlated with smoking. These results suggest that more genetic changes accumulate during tumorigenesis in squamous cell carcinomas than in adenocarcinomas and that unidentified tumor suppressor genes exist on chromosome 9q for squamous cell carcinoma and on chromosome 8q for adenocarcinoma of the lung. These differences may be related to differences in tumorigenic mechanisms, such as etiological factors, operating in the separate histologies.

Adenocarcinoma↗

PubMed1994

PAPNET analysis of reportedly negative smears preceding the diagnosis of a high-grade squamous intraepithelial lesion or carcinoma.

One hundred fourteen cervical smears obtained from 18 women developing biopsy-proven high-grade squamous intraepithelial lesions and two with invasive squamous carcinomas were analyzed by two pathologists using the PAPNET neural network-based automated screening system (PAPNET Analyses A and B). The smears were originally reported as negative and had been previously rescreened and reclassified according to The Bethesda System. Using the PAPNET video displays of 128 potentially abnormal cellular images per smear, each reviewer (PAPNET A and B) determined whether a smear required conventional rescreening. Results of the PAPNET triage were compared with the reclassification diagnoses of the smears by conventional microscopy. PAPNET Analysis A selected eight (14%) smears reclassified as negative, 25 (69%) as atypical squamous cells of undetermined significance, and 15 (71%) as squamous intraepithelial lesions (SIL) for rescreening. In PAPNET Analysis A, two (10%) SILs were not selected for rescreening, and four (19%) were considered unsatisfactory for analysis. PAPNET Analysis B selected 21 (37%) smears reclassified as negative, 25 (69%) as atypical squamous cells of undetermined significance, and 18 (86%) as SIL for review. In PAPNET Analysis B, two (10%) SILs were missed, and one (5%) smear was unsatisfactory for analysis. Each PAPNET analysis selected smears for rescreening in 19 (95%) of 20 patients and detected SILs in 10 patients that were missed in the original screening. Using PAPNET, SILs would have been detected a median of 56 months (PAPNET A) and 62 months (PAPNET B) before their actual discovery. These preliminary data suggest that PAPNET may help detect SILs missed in routine cytologic screening.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinoma, Squamous Cell↗

PubMed1994

Basal cell carcinomas and squamous cell carcinomas of human skin show distinct patterns of chromosome loss.

Although basal cell carcinomas and squamous cell carcinomas are clinically and pathologically distinct, the molecular basis for these differences is not clear. We have used polymorphic microsatellite markers to determine the pattern and extent of chromosome losses in a series of 44 basal cell carcinomas and 47 squamous cell neoplasms of the skin. Basal cell carcinomas showed a distinctive allelotype with chromosome loss largely confined to a single chromosome arm, 9q (26 of 44 informative tumors). In contrast to the predominance of loss on a single chromosome arm in basal cell carcinomas, squamous cell neoplasms showed more widespread loss with loss of heterozygosity of markers from 35 of 39 chromosome arms in one or more of the tumors studied. The pattern of loss was also different from basal cell carcinomas with frequent loss of heterozygosity of markers from 9p (41%), 13q (46%), 17p (33%), 17q (33%), and 3p (23%) in squamous cell neoplasms. The frequent loss of markers from these chromosome arms relative to other chromosome losses suggests that these arms may contain genes important in the development of cutaneous squamous cell carcinomas.

Basal Cell Carcinoma↗

PubMedDate not supplied

Augmentation of interleukin-6 (IL-6) expression in squamous carcinoma cells and normal human keratinocytes treated with recombinant anti-neoplastic protein (ACP).

A protein purified from Eschericheri coli has previously been shown to have cytotoxic effects on neoplastic cells of several lineages both in vitro and in vivo. Accordingly, this protein has been named anti-neoplastic protein (ACP). Although ACP kills neoplastic cells by inducing apoptosis, it has negligible effects on various normal cells. In addition to the direct cytotoxic effects of ACP on tumour cells, previous studies have shown that in vivo ACP increases tumouricidal activity of cytotoxic lymphocytes. We investigated whether cytokines from host or tumour cells play a part in the enhanced cellular immunity seen in ACP-treated tumour-bearing mice. Growth of normal human keratinocytres (KC) was not significantly affected by subnanogram amounts of ACP, however ACP dose-dependently killed KHT cells, a murine fibrosarcoma cell line (LD50 = 8 x 10(4) ng/cell). as well as the human squamous carcinoma cell line COLO-16 (LD50 = 2.5 x 10(-4) ng/cell). Testing purified ACP on cultures of normal keratinocytes and squamous carcinoma cell lines revealed that ACP could induce both mRNA and protein for interleukin-6 (IL-6). Messenger RNA for IL-6 increased dose-dependently 4h after treatment of COLO-16 squamous carcinoma cells with 10(-4) to 10(-2) ng/cell ACP. Maximal increment was 50-fold. Interleukin-6 message remained elevated up to 24h later in both normal keratinocytes and squamous carcinoma cultures treated with ACP. Conditioned supernates from these cultures were analysed by ELISA and found to have 4-fold higher levels of IL-6 protein than untreated cells after 4h. After 24h, IL-6 did not increase above the 4h level. Boiling of the ACP preparation showed that the cytokine induction was not due to contaminating lipopolysaccharide. The cytoxic effect of ACP on tumour cells in vitro was not due to IL-6 protein induction since neither recombinant IL-6, nor the other proinflammatory cytokines, IL-1 alpha or Tumour necrosis factor-alpha (TNF-alpha) (0.1-10ng/ml) were able to kill malignant cells. We demonstrated IL-6 gene induction by ACP in the squamous carcinoma lines as well as in normal KC. This suggests that the in vivo effectiveness of ACP against tumours may be due to stimulatory effects of IL-6 on host immunity.

Antineoplastic Agents↗

PubMed1994

Suppression of squamous cell carcinoma growth and differentiation by retinoids.

The epithelium of the oral cavity is mostly nonkeratinizing. However, it undergoes an abnormal squamous differentiation with keratinization during vitamin A deficiency or oral carcinogenesis. Vitamin A analogues (retinoids) were found to be effective in preventing oral premalignant lesions and second primary cancers in the upper aerodigestive tract. Further development of retinoids for prevention and therapy of squamous cell carcinoma (SCC) requires a better understanding of their mechanism action on the growth and differentiation of SCC cells. We used cultured head and neck SCC (HNSCC) cell lines as a model system. Treatment of HNSCC cells with beta-all-trans-retinoic acid resulted in inhibition of growth (proliferation and colony formation) and suppression of squamous differentiation to varying degrees in the different cell lines. Because some of the malignant HNSCC cells recapitulate the main characteristics of keratinocyte squamous differentiation and responsiveness to retinoids, they can serve as a model for investigating the mechanism underlying the effects of retinoids on cell growth and differentiation. It is thought that nuclear retinoic acid receptors (RARs) and retinoid X receptors (RXRs) mediate the above effects of retinoids by acting as DNA-binding transcription-modulating factors. We found that HNSCC cell lines express several nuclear RAR and that their level could be modulated by retinoids in some cell lines. An inverse relationship was found between RAR-beta expression and squamous differentiation. An analysis of RAR mRNA expression in head and neck cancer specimens revealed a decrease in RAR-beta in premalignant and malignant tissues relative to normal mucosa. The expression of this receptor increased in vivo after treatment with 13-cis-retinoic acid. These results implicate the loss of RAR-beta expression in the development of head and neck cancer and suggest that RAR-beta could serve as an intermediate marker in prevention trials.

Animals↗