Mutagenic mucus in the cervix of smokers

A pilot study was conducted to determine whether any relationship exists between mutagenicity of a women's uterine cervical mucus and her current smoking status. Cervical fluids obtained from 78 premenopausal women seen between July 1983 and March 1984 at the University of California, San Francisco Dysplasia (and diethylstilbestrol) Clinic or in a private practice were tested for mutagenicity by means of the Ames-Salmonella microsomal test. Of 36 current smokers, 14 (39%) had positive tests as compared to 5 of 42 nonsmokers (12%). The odds ratio (OR) estimate was 4.7 with 95% confidence limits (CL) of 1.6-14.2. Secretions from 14 of 32 (44%) women who had smoked during the day of the sample collection--within the previous 7 hours--were positive on the laboratory test, whereas none of the 4 women was positive who had smoked 8 hours or more before the specimens were obtained. Fluids from women with dysplasia or carcinoma in situ were more likely to be mutagenic than were those from other women, although this finding may be due to chance (OR = 2.0 with 95% CL of .70-5.9). This relationship between smoking and mutagenic cervical fluids offers evidence that might help to explain the association between cervical cancer and cigarette smoking noted in previous epidemiologic studies.     

Nicotine and cotinine in the cervical mucus of smokers, passive smokers, and nonsmokers.

Although epidemiological studies suggest that cigarette smoking is a risk factor for cervical cancer, further evidence is required to document the biological plausibility of this relationship. This study obtained cervical mucus, using a cervical flush technique, from 50 patients in a neoplasia clinic. Nicotine was detected in the cervical mucus of all 25 smokers and cotinine in the mucus of 84% of the smokers; nicotine and cotinine levels were correlated (P < or = 0.10) with both the number of cigarettes usually smoked and the number smoked in the last 24 h. Nicotine and cotinine levels for passive smokers and nonexposed women were much lower than for women who currently smoked, with little difference found between the nonsmoking women who did and did not report passive smoke exposure. In the one woman who reported smokeless tobacco use, both nicotine and cotinine were detected at much higher levels than for other nonsmoking women. These results indicate that tobacco constituents do indeed reach the uterine cervix, suggesting that they could play a causal role in the development of cervical cancer.     

On the mutagenic action of adenine

The deamination of cytosine and adenine is mutagenic; the deamination of guanine is not. The deamination of cytosine leads to G = C → A = T point mutation and to G → A and C → T transition in the DNA molecule; the deamination of adenine leads to the opposite A → G and T → C transition. It is shown that adenine lack could be as mutagenic as adenine deamination and it is also shown schematically that adenine lack through defective adenine synthesis could give rise to a population of genetically abnormal cells incapable of any degree of differentiation, a state perhaps reminiscent of the most acute of leukaemias and the most anaplastic of cancers.     

Adenocarcinoma in situ of the cervix

BACKGROUND: The current study examines 1) the sensitivity of detection and 2) sampling and screening/diagnostic error in the cytologic diagnosis of adenocarcinoma in situ (AIS) of the cervix. The data were taken from public and private sector screening laboratories reporting 25,000 and 80,000 smears, respectively, each year. METHODS: The study group was comprised of women with a biopsy diagnosis of AIS or AIS combined with a high-grade squamous intraepithelial lesion (HSIL) who were accessioned by the Western Australian Cervical Cytology Registry (WACCR) between 1993-1998. Cervical smears reported by the Western Australia Centre for Pathology and Medical Research (PathCentre) or Western Diagnostic Pathology (WDP) in the 36 months before the index biopsy was obtained were retrieved. A true measure of the sensitivity of detection could not be determined because to the authors' knowledge the exact prevalence of disease is unknown at present. For the current study, sensitivity was defined as the percentage of smears reported as demonstrating a possible or definite high-grade epithelial abnormality (HGEA), either glandular or squamous. Sampling error was defined as the percentage of smears found to have no HGEA on review. Screening/diagnostic error was defined as the percentage of smears in which HGEA was not diagnosed initially but review demonstrated possible or definite HGEA. Sensitivity also was calculated for a randomly selected control group of biopsy proven cases of Grade 3 cervical intraepithelial neoplasia (CIN 3) accessioned at the WACCR in 1999. RESULTS: For biopsy findings of AIS alone, the diagnostic "sensitivity" of a single smear was 47.6% for the PathCentre and 54.3% for WDP. Nearly all the abnormalities were reported as glandular. The sampling and screening/diagnostic errors were 47.6% and 4.8%, respectively, for the PathCentre and 33.3% and 12.3%, respectively, for WDP. The results from the PathCentre were better for AIS plus HSIL than for AIS alone, but the results from WDP were similar for both groups. For the CIN 3 control cases, the "sensitivity" of a single smear was 42.5%. CONCLUSIONS: To the authors' knowledge epidemiologic studies published to date have not demonstrated a benefit from screening for precursors of cervical adenocarcinoma. However, in the study laboratories as in many others, reasonable expertise in diagnosing AIS has been acquired only within the last 10-15 years, which may be too short a period in which to demonstrate a significant effect. The results of the current study provide some encouraging baseline data regarding the sensitivity of the Papanicolaou smear in detecting AIS. Further improvements in sampling and cytodiagnosis may be possible.     

Adenocarcinoma of the cervix

BACKGROUND: The current study examines 1) the sensitivity of detection of invasive adenocarcinoma of the cervix in a routine cervical screening service, and 2) the frequency in smears of cytologic criteria previously found to be useful in diagnosis. METHODS: Data on women with diagnoses of adenocarcinoma of the cervix accessioned at the Western Australian Cervical Cytology Registry during the period 1993-1998 were examined, where smears had been reported by Western Diagnostic Pathology within three years of the biopsy diagnosis. Smears and biopsy material were reviewed. RESULTS: Thirty-six smears from 24 women were reviewed. Of those, 58.3% had been reported as a possible or definite high grade epithelial abnormality (HGEA). On review it was thought that this could be improved to 77.8%. The screening or diagnostic error was thus 19.4% and the sampling error 22.2%. The likelihood of an individual woman receiving a report of a possible or definite HGEA in the three years before biopsy was 83.3%. In retrospect this could have been improved to 91.7%. Heavy bloodstaining with abundant abnormal glandular epithelium (14 smears) and small three-dimensional or papillary clusters (16 smears) were the most frequent clues to invasion. Tumor necrosis/diathesis was present in eight smears, but easily seen in only four, while marked nuclear pleomorphism and macronucleoli were seen in three and one smears respectively. In cases with a discrepancy between the initial and the review findings, very small amounts of abnormal material (three smears), a resemblance to endometrial cells (one smear), and an unusual appearance of folded monolayered sheets (three smears) contributed to the difficulty of diagnosis. CONCLUSIONS: There were significant sampling and screening/diagnostic errors (22.2% and 19.4%, respectively). Screening and diagnostic errors could perhaps be reduced by a greater awareness of the range of cytologic changes, but these may be subtle. Heavy bloodstaining with abundant abnormal glandular material may be a useful clue to invasive, rather than in situ, adenocarcinoma, even in the absence of tumor diathesis or fully malignant nuclear criteria.     

Adenocarcinoma of the cervix

Opinion statement Cervical adenocarcinomas are increasing in incidence each year, comprising up to 25% of all cervical cancers diagnosed in the United States. This increase largely reflects the inherent difficulty in detecting glandular precursor lesions using current screening practices. However, there also appears to be a recent shift in the epidemiology of the disease process with younger women being diagnosed more frequently. Fertility-sparing surgery is an option for selected patients with adenocarcinoma in situ or stage IA₁ cervical adenocarcinoma. Simple hysterectomy should be performed at the completion of childbearing or when preserving fertility is not an issue. The treatment of choice for most women with stage IA₂ to IB₁ disease is radical hysterectomy. Fewer than 20% of patients will need adjuvant therapy and the cure rate is excellent. Primary radiation with weekly cisplatin may be the best option for patients with stage IB₂ to IIA cervical adenocarcinoma. Patients treated initially by primary radical surgery will almost certainly require postoperative chemoradiation because of high-risk surgical-pathologic features. Patients with stage IIB to IVA disease should also receive primary radiation with weekly cisplatin. Management of recurrence should be individualized, depending on the location of disease and the type of previous therapy.     

Histochemical study of the mucus in villous tumors of the colon

The study deals with a comparative histochemical evaluation of mucus secreted by normal large bowel mucosa and that obtained from 10 villous tumors (colorectal adenoma--6 and colorectal adenocarcinoma--4). Level of production and chemical composition of mucus changed with tumor advancement: an increase in neutral mucopolysaccharides synthesis was matched by lowered production of acid ones. Also, deranged sulphatation of mucus and changes in sialomucin profile were established.     

Tumour size in cancer of the cervix

In a randomized trial comprising 204 patients with operable cervical carcinomas stages I and II, two low-dose rates in gynaecological brachytherapy were compared. Treatment consisted of Cs-137 uterovaginal application followed by surgery (either immediate or delayed). The results for the two dose rates have been published previously. The present paper concerns the correlation between outcome and tumour size. Tumour size was carefully estimated in two ways: by clinical examination under general anaesthesia and by measurements on the customized vaginal mould used for the brachytherapy. Ninety-one patients (45%) were classified as stage I, and 113 were classified as stage II proximal. The mean tumour size was 39 mm (range 15-64 mm). Cox's multivariate analysis indicated that the factors with a poor prognostic value were for survival: node involvement (N +) (p < 0.001), large tumour size (T +) (p < 0.001) and involvement of the endocervix (E +) (p <0.01); for event-free survival: N + (p <0.001), T + (p < 0.001); for local control; N + (p = 0.0001); for metastasis and regional relapse: N + (p < 0.001) and T + (p < 0.001). Stage was not a prognostic factor over the present range in either univariate or multivariate analysis. In this series tumour size is a powerful independent prognostic factor. It is therefore suggested that for the classification of cervical cancer and the indications for surgical staging and adjuvant treatment, tumour size should be taken into account.     

Multiplicity of abnormal promoter methylation in lung adenocarcinomas from smokers and never smokers

The prevalence of methylation of the p16, DAPK and RASSF1A genes was investigated in lung adenocarcinoma from smokers, former uranium miners and never smokers. The association between a common genetic alteration in adenocarcinoma, mutation of the K-ras gene and methylation of these genes, as well as survival was examined. Adenocarcinomas from 157 smokers, 46 never smokers and 34 former uranium miners were evaluated for methylation of the p16, DAPK and RASSF1A genes using the methylation-specific PCR assay. Comparisons were also made to prevalences of methylation of the MGMT gene and mutation of the K-ras gene previously examined in these tumors. The prevalence of methylation for all genes was similar between adenocarcinomas from smokers and never smokers, although the prevalence for methylation of the p16 gene tended to be higher in smokers compared to never smokers. A significantly higher prevalence for p16 methylation was seen in central vs. peripheral lung tumors. At least 1 gene was methylated in 35% of stage I tumors, whereas 2 and >/=3 genes were methylated in 40% and 16% of tumors, respectively. Methylation of all genes was independent of K-ras mutation, whereas methylation of the DAPK and RASSF1A genes was positively associated. Environmental tobacco smoke, the strongest lung cancer risk factor among never smokers, induces adenocarcinoma in part through inactivation of the p16, DAPK and RASSF1A genes. Adenocarcinomas may develop through 2 distinct processes: multiple gene inactivations through promoter hypermethylation and activation of the K-ras gene.     

Adenocarcinoma of the uterine cervix

In Finland, the incidence of cervical cancer has shown a decreasing tendency since the 1960s. The same trend, however, has not been noticed in the incidence of cervical adenocarcinoma. The reason for this is not known, although many studies have shown differences in the cause, epidemiology, and biology of the epidermoid and adenocarcinoma of the uterine cervix. A total of 106 new patients with cervical adenocarcinoma were treated at our institution from 1976 to 1980, which represents 20.4% of all cervical carcinomas treated. The mean age of the patients was 58.1 years (range, 29 to 82 years) and the peak incidence was in the group 60 to 69 years of age. Most of the patients were postmenopausal (71.7%) and the main symptom was abnormal vaginal bleeding (78.3%). The proportion of Stage I was 61.3%. Combined operative and radiation therapy was used in 74.5% of the patients. The overall 5-year survival rate was 65.1% (corrected 74.5%), which did not differ from that of patients with squamous cell carcinoma. The most significant prognostic factors were the size of the tumor, presence of pelvic lymph node metastases, and the stage of the disease.