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Schistosomiasis, metaplasia and squamous cell carcinoma of the prostate: histogenesis of the squamous cancer cells determined by localization of specific markers.

Histogenesis of squamous cell carcinoma in two prostates heavily affected by schistosomiasis was determined immunohistochemically by localization of two prostatic specific markers and keratin. The demonstration of prostatic specific antigen and keratin served to differentiate between metaplasia and squamous cell carcinoma associated with prostatic schistosomiasis from other prostatic and urinary bladder neoplasms.

Acid Phosphatase↗

[Relevance of the new tumor marker SCC (squamous cell carcinoma antigen) for the diagnosis and follow-up control of squamous epithelial carcinoma of the head and neck].

The SCC antigen, a tumour marker for squamous cell carcinoma, is already used for the diagnosis and follow-up of carcinoma of the cervix and the lungs. We determined the SCC antigen levels at the time of diagnosis and during therapy in 108 subjects with a squamous cell carcinoma of the head and neck. According to our results and those of other authors, the normal serum range of SCC lies between 0 and 2 ng/ml. Before therapy we found an increased titre in 38.9% of the subjects, being 6.2%, 30.8%, 47.2% and 76.2% for stages T1 to T4 respectively. Thus even some stage T3 and T4 tumours did not express the antigen. No correlation was found between the titre at the time of diagnosis and the grade of differentiation, the site of the tumour, the presence of lymph node or remote metastases, and the sex of the patient. After operation the titres returned to normal within 1 week, but after radiation or chemotherapy the titre decreased more slowly. In recurrent tumours we found a rising titre, which could be measured in several cases some weeks before the recurrence was visible. In the light of the costs and the yield of the method, we suggest determining the serum SCC antigen level once before therapy. If it is increased, subsequent estimates should be done during the succeeding years to allow early diagnosis of a recurrence of the tumour.

Antigens, Neoplasm↗

[A comparism between lysosomal enzyme activity in normal ectocervical squamous epithelium and squamous carcinoma of the ectocervix].

A comparative study was made of the total lysosomal enzyme activity found in homogenates of normal ectocervical squamous epithelium and squamous carcinoma of this epithelium. The activities of acid phosphatase, beta-glucuronidase, cathepsin D and acid ribonuclease were higher in carcinoma tissue than in normal tissue. The most important observation made was with regard to the distribution of enzyme activity in homogenates. In carcinoma homogenates most of the enzyme activity was detected in the lysosomal fractions, whereas in controls the activity was predominantly found in the cytosol fractions. No histochemical and electron microscopical techniques were used in this study. Because it was possible to sediment the enzyme activity and to demonstrate latency, these can be referred to as lysosomal enzymes with certainty.

Acid Phosphatase↗

Image analysis of atypical bronchial squamous epithelial cells. A quantitative and qualitative examination of squamous cell carcinogenesis.

Atypical bronchial squamous epithelial cells from cigarette smokers were digitized using a high-resolution microphotometric scanning system operating at a wavelength of 530 nm. All cells used for the purpose of developing a training set as well as those used as a test set were classified by a team of three cytopathologists. Reduction in the dimensionality of the feature space and cell classification were performed using a new system known as the atypia status index (ASI); this dual-purpose system will specifically classify cells into five distinct classes of progressive atypia as well as quantitate the degree of atypicality of each individual cell. The distribution of cellular ASI values was arranged from lowest to highest and plotted for each subject as a profile. The ASI range has well-defined intervals, representing the five different atypia classes used in the study (squamous metaplasia, mild atypia, moderate atypia, severe atypia and carcinoma). Subjects at different stages of carcinogenesis were found to have significantly different profiles (P less than 0.01). Changes in visual morphologic characteristics and their relation to changes in ASI values for the five different classes of atypia are presented.

Bronchi↗

[Immunohistochemical study on the expression of carbohydrate antigens in normal squamous epithelia and squamous cell carcinomas of the uterine cervix].

The expression of 4 kinds of carbohydrate antigens, CA50, CA19-9, sialyl SSEA-1, and DU-PAN-2 was studied immunohistochemically in 15 normal cervical squamous epithelia and 49 cervical carcinomas. (1) In normal epithelia, CA50 and CA19-9 were expressed in all cell layers and all cell layers except for the basal layer, respectively, and a gradual decrease in the intensity of staining was observed in the upper layer. Sialyl SSEA-1 was expressed only in the superficial layer, but DU-PAN-2 was not found in any normal epithelia. (2) In cervical carcinomas, CA50, CA19-9, sialyl SSEA-1 and DU-PAN-2 were observed in 51.0%, 49.0%, 55.1% and 26.7%, respectively. (3) The number of Ki67 positive cells tended to be lower in the area with sialyl SSEA-1 immunostaining. (4) In the cases in which sialyl SSEA-1 positive cells were distributed diffusely in cancer nests, the incidence of lymph node metastasis was significantly higher. These result suggest that the expression of CA50, CA19-9 and sialyl SSEA-1 is related to the differentiation of normal squamous epithelial cells, and sialyl SSEA-1 may be related to cell differentiation also in cervical carcinomas, and the features of its expression may be useful in predicting the biologic properties of cervical carcinomas.

Adult↗

Harvey ras (H-ras) point mutations are induced by 4-nitroquinoline-1-oxide in murine oral squamous epithelia, while squamous cell carcinomas and loss of heterozygosity occur without additional exposure.

Tumorigenesis is a multistep genetic process requiring several somatic mutations for neoplastic transformation. These mutations appear to be sequential, random, and independent events. However, we find linked, nonrandom ras mutations occurring during 4-nitroquinoline-1-oxide-induced tumorigenesis months after exposure to the carcinogen had ceased. The carcinogen had been topically applied to the oral cavity of CBA mice for 4 to 16 weeks. Dysplasia developed after 24 weeks, and carcinoma in situ and squamous cell carcinoma developed after 28 weeks. H-ras mutations were detected in 13 of 25 tissue specimens (10 of 14 invasive carcinomas and 2 of 4 carcinoma in situ, 1 of 5 dysplastic tissue, and 0 of 2 normal tissues). Approximately one-half of the tumors had G to A point mutations at codon 12 of the cellular H-ras proto-oncogene on mouse chromosome 7. None had codon 11, 13, or 61 mutations. Loss of heterozygosity occurred in 5 of 14 invasive cancers. Larger invasive squamous cell carcinomas consistently lost the wild-type allele, whereas preneoplastic lesions and small tumors were heterozygous for ras. This suggests a causal relationship between carcinogen treatment, H-ras activation, and initiation of tumorigenesis. The wild-type allele in mouse chromosome 7 is lost with the progression of tumorigenesis long after exposure to the carcinogen. Thus, loss of heterozygosity of the ras gene appears to occur without multiple carcinogen-induced mutations, i.e., as a result of a cascade of events induced by an earlier ras mutation.

4-Nitroquinoline-1-oxide↗

Human immunodeficiency virus-associated squamous cell carcinomas of the head and neck presenting as oral and primary intraosseous squamous cell carcinomas.

Six cases of squamous cell carcinoma arising in the head and neck of patients infected with the human immunodeficiency virus are described. This article reports the first two cases of primary intraosseous squamous cell carcinoma associated with infection with human immunodeficiency virus. Clinical presentation, results of imaging studies, histologic characteristics, therapies applied, and the clinical follow-up are described in detail for each of the six cases. These data are evaluated through a review of the current literature.

Acquired Immunodeficiency Syndrome↗

Differential expression of the monocyte chemoattractant protein-1 gene in human papillomavirus-16-infected squamous intraepithelial lesions and squamous cell carcinomas of the cervix uteri.

Monocyte chemoattractant protein (MCP)-1 is an important factor involved in the cross-talk between mononuclear cells and human papilloma-virus (HPV)-infected cervical epithelia. To prove the experimental model of a negative regulatory loop between the expression of the HPV oncogenes E6/E7 and the MCP-1 gene in vivo, we examined HPV-16-infected conization/hysterectomy specimens consisting of 6 low- and 6 high-grade squamous intraepithelial lesions (SILs) and 5 squamous cell carcinomas (SCCs) as well as the adjacent mucosa by isotopic RNA in situ hybridization. Langerhans cells and stromal macrophages were identified by the antibodies S-100 and PG-M1. E6/E7 expression was restricted to dysplastic or neoplastic keratinocytes, whereas MCP-1 transcripts were detectable in normal, dysplastic, and neoplastic epithelia, in endothelia, and in stromal macrophages. Langerhans cells were always negative. MCP-1 expression was predominant at the epithelial-mesenchymal junctions and especially intense when the stromal macrophage reaction was increased. Generally, the synchronous expression of E6/E7 and MCP-1 was very rare in SILs (2 of 12 cases). In high-grade SIL, MCP-1 expression was observed in 1 of 6 cases, whereas all lesions strongly hybridized with E6/E7 probes. In contrast, 4 of 5 SCCs re-expressed MCP-1, and 2 cases revealed marked transcriptional activities for both E6/E7 and MCP-1. Although preliminary, our observations lend support to the suggestion that the experimental model of transcriptional regulation and exclusion of either HPV E6/E7 or MCP-1 expression is especially pertinent to high-grade SIL, whereas in most SCCs, other environmental factors may influence this relationship.

Base Sequence↗

Clinical Significance of a cervical cytologic diagnosis of atypical squamous cells of undetermined significance. Favoring a reactive process or low grade squamous intraepithelial lesion.

OBJECTIVE: To define the clinical significance of qualifying the cytologic diagnosis of atypical squamous cells of undetermined significance (ASCUS) as favoring either a reactive process or a low grade squamous intraepithelial lesion (LSIL) in an effort to provide management guidelines. STUDY DESIGN: A total of 118 consecutive nonpregnant women with a cytological diagnosis of ASCUS favoring either a reactive process or LSIL were evaluated in our colposcopy clinic by repeat cervical cytologic smear, colposcopy and colposcopically directed biopsies and/or endocervical curettage, as indicated. RESULTS: Of the 58 patients evaluated for a smear of ASCUS, favoring a reactive process, 5 (8.6%) had cervical intraepithelial neoplasia (CIN) CIN 1 documented by biopsy. None had a high grade lesion. Twenty-six (45%) of the 58 patients who had a cytologic diagnosis of ASCUS favoring a reactive process had a repeat smear that was normal. None was found to have CIN. Of the 60 patients who had a cervical diagnosis of ASCUS favoring LSIL, 9 (15%) had CIN 1 or CIN 2. Nineteen (32%) of the 60 patients who had a cytologic diagnosis of ASCUS favoring LSIL had a repeat smear that was normal. One of these patients had CIN 1 on biopsy. The sensitivity of a repeat smear, in this limited series, after an initial smear of ASCUS favoring a reactive process is 100%, while it was 66% after an initial smear of ASCUS favoring LSIL. CONCLUSION: This study showed that in our laboratory a cytologic diagnosis of ASCUS favoring either a reactive process or LSIL is associated with a very low risk that the patient is haboring CIN. In the patient whose initial smear shows ASCUS favoring a reactive process, a repeat smear that is normal is reassuring. The patient whose smear shows ASCUS favoring LSIL probably requires further evaluation even in the presence of a normal repeat smear.

Adolescent↗

Microglandular hyperplasia has a cytomorphological spectrum overlapping with atypical squamous cells-cannot exclude high-grade squamous intraepithelial lesion (ASC-H).

We retrospectively evaluated cytological interpretations of conventional cervical smears in 48 cases of biopsy-proven microglandular hyperplasia and compared them with 15 negative controls. A glandular pattern was noted in all 48 cases but was predominant in 73% (35/48) of the cases. Immature metaplastic pattern was present in 71% (34/48) and was predominant in 27% (13/48). These features were not observed in negative control smears. 85% of cases (41/48) were interpreted as negative for epithelial cell abnormality. Two cases with predominantly glandular pattern (6%, 2/35) were interpreted as atypical glandular cells. Five cases with predominantly immature metaplastic pattern (38%, 5/13) showed checkerboard arrangement or rows of single cells with slightly larger atypical nuclei leading to interpretation as "atypical squamous cells-cannot exclude high-grade squamous intraepithelial lesion." The metaplastic cells with normoblast-like karyorrhectic apoptotic debris confined to the nuclear area were scattered among these cells in microglandular hyperplasia with metaplastic pattern.

Adult↗

Pap smear screening in an equal-access health care system. Yield of screening and predictors of squamous intraepithelial lesions and atypical squamous cells of undetermined significance.

PURPOSE: The purpose of this study was to examine predictors of squamous intraepithelial lesions (SIL) and atypical squamous cells of undetermined significance (ASCUS) in an equal access health care setting.METHODS: A cohort of 10,713 active-duty United States Air Force women who provided one cervical/vaginal smear (CVS) as part of routine medical care between January 1, 1994 and December 31, 1996 were selected for this study. Each of the specimens was characterized by a "Bethesda System" diagnosis: within normal limits, repair/reactive, ASCUS, low grade SIL, high grade SIL, invasive carcinoma, infectious disease or unsatisfactory.RESULTS: Significant disease was associated with age younger than 30 years, enlisted rank, Hispanic ethnicity and the presence of genital warts on examination. SIL was associated with age 21-25 and Hispanic ethnicity in the logistic regression model. A diagnosis of ASCUS was associated with age younger than 30, marital status as single/never married, presence of genital warts on physical examination, and a history of previous abnormal CVS since entering military service. Age younger than 30, a marital status of single/never married and a previous abnormal CVS were associated with ASCUS in the logistic regression model.CONCLUSIONS: The disparity noted between women of low and high socioeconomic status was not seen here; those with the lowest income and education were not significantly more likely to have SIL or ASCUS when age was considered in the model. The significant association between Hispanic ethnicity and SIL, which should be further explored, may indicate the need for increased screening in this population.

Journal Article↗

The use of endocervical curettage in women with low-grade squamous intraepithelial lesions or atypical squamous cells of unknown significance on Pap smear.

OBJECTIVE: To determine the use of endocervical curettage in women with low-grade squamous intraepithelial lesions (LSIL) or atypical squamous cells of unknown significance (ASCUS) on Pap smear. METHODS: A cross-sectional study evaluated women at a single center colposcopy service between January 1999 and December 2003 having LSIL or ASCUS on Pap smear and compatible lesions on colposcopic examination who underwent endocervical curettage. Associations of abnormal endocervical curettage results with lesion topography, age, and satisfactory colposcopy were evaluated. A multivariate logistic regression model was used to evaluate independent associations and estimate the probabilities of abnormal endocervical curettage for different clinical scenarios. RESULTS: Two hundred thirty-seven women were included. The estimated prevalence of abnormal endocervical curettage was 5.5% (95% CI = 2.6%-8.3%). Only 2 endocervical curettage results reported cervical intraepithelial neoplasia 2 or 3 (0.8%, 95% CI = 0%-2%). Bivariate analysis showed a significant association between abnormal endocervical curettage result and central topography of the lesion (p = .01). A multivariate logistic regression analysis confirmed that association (p = .04). The model was used to calculate probabilities of abnormal results in different scenarios. CONCLUSIONS: The overall prevalence of abnormal endocervical curettage in patients with LSIL or ASCUS on Pap smear is low. The prevalence of endocervical curettage results reporting cervical intraepithelial neoplasia 2 or 3 lesions is even lower. Therefore, the use of systematic endocervical curettage performance in this setting is questionable. Our model helps to predict the probability of abnormal results and assist in the decision of whether to perform endocervical curettage.

Adolescent↗

Diagnosis and survey of abnormal/atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesions: a retrospective study.

The new Bethesda System (BS) terminology has opened a series of problems about the Abnormal/Atypical Squamous Cells of Undetermined Significance (ASCUS) and Low-Grade Squamous Intraepithelial Lesion (L-SIL) categories, particularly on their treatment and follow-up. Moreover in these field a non negligible portion of lesions progress to High-Grade Lesion (H-SIL). With the aim of comparing the data, we examined samples observed in our Ambulatories with 6-12 months follow-up. We observed retrospectively 11.197 Pap test from January 1995 to June 1997, mostly first visits. All received a Pap test, colposcopy and gynaecological examination. Biopsy and histological standard examinations were performed when necessary. Alterations classified as mild epithelial abnormalities, of both ASCUS and L-SIL categories, were observed in 146 cases: 78 ASCUS and 68 L-SIL. Of these 48 were CIN 1/mild dysplasia (25 HPV associated) and 20 were HPV lesions, according to BS. All the cases with persistent ASCUS and L-SIL underwent a second control. In these 45 cases we observed 2 new cases of H-SIL and one of L-SIL; so 82.3% and 30.7% of ASCUS and L-SIL regressed to negatives. In the stable group 11.8% and 60.4% were ASCUS and L-SIL. Moreover 5.9% of ASCUS and 4.8% of L-SIL progressed to H-SIL. No cases of invasive cancer were observed. Our data show that ASCUS and L-SIL diagnosis can identify 6% and 4.8% of H-SIL respectively. In addition 17-18% of ASCUS were stable or progressed. These two categories, as already demonstrated in other studies, are mostly at risk.

Cervix Uteri↗

Plasma levels of a squamous cell carcinoma-associated antigen in athymic nude mice bearing human squamous cell carcinoma xenografts of oral origin. With preliminary clinical data.

A human squamous cell carcinoma (SCC) of oral origin was transplanted into athymic mice that were then divided into six groups. The mice were killed at 1 to 6 weeks after tumor transplantation; the sixth group was killed 1 week after excision of SCC grafts. Plasma samples were obtained from each mouse at the time of death for the determination of SCC-associated antigen (SCCAA), a cytoskeletal protein fraction of about 48,000 daltons originally derived from SCC of the uterine cervix. The plasma SCCAA level rose gradually and proportionately to the growth of SCC xenografts from a baseline of 0.66 ng/ml [standard error (SE) + 0.12] to the preoperative peak of 8.44 ng/ml (SE + 1.86) at 5 weeks, to fall precipitously to the postoperative level of 1.05 ng/ml (SE + 0.27) at 6 weeks. No rise in plasma SCCAA level was observed in mice bearing a human malignant melanoma, and only modest rises were observed in mice bearing human adenocarcinomas and oat cell carcinoma. In this experimental model rising plasma SCCAA levels were found to be dependable indicators of SCC tumor growth. These observations and preliminary data on SCCAA levels in patients with or without SCC of the head and neck lend support to the clinical usefulness of serial plasma SCCAA determinations in monitoring patients with SCC of the oral cavity.

Animals↗

Squamous cell carcinoma antigen in the diagnosis and treatment follow-up of oral and facial squamous cell carcinoma.

The squamous cell carcinoma (SCC) antigen was determined by radioimmunoassay in the serum of 40 untreated patients with SCC of the oromaxillofacial region. The mean (+/- SEM) serum concentration for these patients (3.8 +/- 0.8 ng/ml) was significantly higher than that of 52 disease-free patients coming to routine postoperative care (1.2 +/- 0.1 ng/ml) and of 74 healthy controls (1.1 +/- 0.07 ng/ml). Using a arbitrary limit of 2.2 ng/ml, pathologic serum levels of SCC were observed in 15 (38%) of 40 untreated patients, whereas only four (7.7%) of 52 tumor-free patients revealed an elevated serum SCC. Serial measurements of SCC were pretherapeutically available in 28 patients as well as during individual therapy and further follow-up. All but one of these patients had a normal serum SCC postoperatively. The authors' results demonstrate that the clinical value of SCC lies mainly in monitoring the course of the disease. Careful follow-up studies should be undertaken to determine whether serial determination of SCC is promising in early prediction of tumor reoccurrence.

Antigens, Neoplasm↗