Claes Klintenberg

Adenocarcinoma of the ethmoid sinuses. A review of 28 cases with special reference to wood dust exposure

Adenocarcinoma makes up only a small percent of all nasal and paranasal sinus carcinomas, and is most often found in the ethmoid sinuses. Adenocarcinoma of the ethmoid sinuses is known to be associated with exposure to wood dust. Twenty‐eight patients with ethmoid adenocarcinomas were collected, mainly during the last decade from a region with approximately 900,000 inhabitants and with a large amount of furniture industries. There were 4 women and 24 men in the study. Twenty of the men were exposed to dust from hardwood for 20 to 55 years (mean, 40 years) which is in accord with other reports and supports data on the increased risk for workers of developing adenocarcinoma of the ethmoid sinuses when exposed to dust from hardwood. Radiologic diagnosis is necessary to delineate the extent of these tumours, and computerized tomography (CT) especially furnishes important information. Most patients received preoperative radiotherapy followed by surgery, 50% of them survived 5 years, which is in accord with other reports.

p53 status: an indicator for the effect of preoperative radiotherapy of rectal cancer

BACKGROUND Rectal carcinoma is a common malignancy, with a history of high local recurrence rates following surgery. In recent years. preoperative radiotherapy and refined surgical technique have improved local control rates. AIM To investigate the relationship between expression of nuclear p53 protein and the outcome in rectal carcinoma, with and without short-term preoperative radiotherapy. MATERIAL Specimens from 163 patients from the Southeast Swedish Health Care region included in the Swedish rectal cancer trial between 1987-1990. METHOD New sections from the paraffin blocks of the preoperative biopsy and the surgical specimen were examined immunohistochemically using a p53 antibody (PAb 1801). RESULT Expression of nuclear p53 protein was seen in 41% of the tumours. The p53 negative patients treated with preoperative radiotherapy had a significant reduction of local failure compared with the non-irradiated p53 negative patients (P = 0.0008). In contrast, p53 positive patients showed no benefit from preoperative radiotherapy. The interaction between p53 status and the benefit of radiotherapy was statistically significant (P = 0.018). CONCLUSION Expression of nuclear p53 protein in rectal carcinoma seems to be a significant predictive factor for local treatment failure after preoperative radiotherapy. Further investigations are necessary to select patients for preoperative treatment based on analysis of the preoperative biopsies.

Prognostic value of DNA ploidy and S-phase fraction in relation to estrogen receptor content and clinicopathological variables in primary breast cancer.

Tumors from 472 women with primary breast cancer were analyzed by flow cytometry. Divided into four categories, DNA ploidy showed significant association with disease recurrence and mortality. When allowance was made for its correlation with nodal status and estrogen receptor (ER) content, DNA ploidy did not add prognostic information. S-phase fraction was estimated in 290 DNA histograms. In contrast, it was significantly related to recurrence and mortality when controlling for nodal status, tumor size and ER content. When the follow-up was divided into two periods DNA ploidy and S-phase fraction showed association with disease recurrence in the first period only (less than 2.5 years), while the association with mortality was valid for both periods. Light scatter was measured in 234 samples. A low light scatter variability for the stemline nuclei was related to a high recurrence rate during the early follow-up period. In conclusion, DNA flow cytometry adds prognostic information concerning breast cancer patients.

DNA measurement – an objective predictor of response to irradiation? A review of 24 squamous cell carcinomas of the oral cavity

DNA measurements on biopsy material from 24 squamous cell carcinomas of the oral cavity given preoperative radiotherapy indicate that DNA aneuploid tumours respond better to radiotherapy than do diploid and polyploid tumours. The mean S-phase value was higher (16.1%) for 8 tumours that were eradicated by preoperative radiotherapy than for 13 that did not respond (8.1%). These factors correlated better with the response than did histological and clinical (T) classifications. DNA-ploidy and S-phase estimation can complement the histological diagnosis, and may prove valuable when planning treatment.

A comparison of static cytofluorometry and flow cytometry for the estimation of ploidy and DNA replication in human breast cancer

Summary332 primary invasive breast carcinomas were analysed by static cytofluorometry and flow cytometry. The ploidy distributions were similar, and 54% of the tumors were judged DNA aneuploid by both methods.The coefficient of variation of the G0–G1 peaks ranged from 2.0 to 8% with both techniques, but the mean was somewhat lower with flow cytometry — 4.1%, compared to 4.9% for the static measurements.The proportion of S-phase cells was possible to estimate from 80% of the flow histograms and 70% of the static histograms. S-phase was not estimated from the static histograms if less than 150 tumor cells were measured. With 160 tumors S-phase was measured by both methods. The range was 0 to 27% with the static measurements and 0.7 to 25% with flow cytometry. Corresponding mean values were 7.6% and 8.2%, which are similar to thymidine labeling index results with breast cancers reported in some studies. A close correlation was obtained (r = 0.927) comparing S-phase fractions estimated from aneuploid tumors with flow cytometry and static cytofluorometry if more than 200 cells were measured with the latter. The proportion of S-phase cells was significantly lower for the diploid tumors.We conclude that both techniques can be useful for the estimation of DNA ploidy and replication in human breast cancer.

Nasal cuboidal metaplasia with dysplasia. Precursor to adenocarcinoma in wood-dust-exposed workers?

The histological study of the non-tumours nasal mucosa in 22 wood-workers with ethmoidal adenocarcinoma was carried out and special attention was paid to the presence of cuboidal metaplasia with or without dysplasia. The workers had been exposed to wood dust for an average of 38 years (range 18 to 55 years). In 19 cases cuboidal metaplasia was found and 16 of these also had dysplasia. In 10 cases there was a transitional zone with dysplastic cuboidal epithelium in continuity with the tumour. In 5 cases there was squamous metaplasia. The results indicate cuboidal metaplasia with dysplasia being a possible precursor to nasal adenocarcinoma in workers exposed to wood dust, similar to the findings of squamous metaplasia and squamous cell carcinoma in nickel workers.

DNA DISTRIBUTION, CYTOSOL ESTROGEN RECEPTORS AND AXILLARY NODES AS PROGNOSTIC PREDICTORS IN BREAST CARCINOMA

One hundred and fifty patients with breast carcinoma were examined to compare axillary node status, estrogen receptor level and cellular DNA content as prognostic indicators. Seventy-four per cent of the patients were postmenopausal and forty per cent had axillary node metastases. Estrogen receptor was measured by isoelectric focusing in polyacrylamide gel. DNA was measured in individual cell nuclei by means of Feulgen-acriflavine-sulphate stained imprints. Fifty-two per cent of the tumors had diploid and/or tetraploid DNA pattern, and the rest aneuploid pattern. Axillary node metastases, aneuploid DNA pattern and low level of estrogen receptor were related to recurrence. When introduced into Coxs proportional hazards procedure, axillary nodes and estrogen receptor level but not DNA pattern remained as significant predictors of recurrence.

Primary Radiotherapy of Tl and T2 Glottic Carcinoma: Analysis of treatment results and prognostic factors in 223 patients

Treatment results in 223 patients with T1 and T2 glottic carcinoma were analysed. A multivariate analysis was performed to evaluate the prognostic significance of factors related to tumour, patient and treatment. Locoregional control after radiotherapy was 90% for 129 patients with T1 tumours and 73% for 94 with T2 tumours. Disease-specific survival was 96% and 81% for patients with T1 and T2 tumours, respectively. In the multivariate analysis of locoregional control, subglottic extension contributed prognostic information to T-stage. In the univariate analysis, number of involved tumour sites, cord mobility and treatment interruption had a significant influence, which was lost in the multivariate analysis. Age gave additional prognostic information in the multivariate analysis of disease-specific survival. Significant adverse effects of radiotherapy were found in 9 patients (4%). Forty-nine patients (22%) had a second malignancy, 11 (5%) diagnosed before the glottic carcinoma.

Preoperative Irradiation in Oral Cavity Carcinoma: A study with special reference to DNA pattern, histological response and prognosis

The relation between DNA pattern and response to preoperative radiotherapy was studied in 51 patients with oral squamous cell carcinomas operated 4 weeks after irradiation. Small tumors (T1 and T2) showed more pronounced response to radiotherapy than larger ones (T3 and T4), as did DNA aneuploid tumors. Eight of 11 DNA aneuploid tumors showed no remaining tumor in the operation specimen, compared to 6 of 21 DNA polyploid and 2 of 19 DNA diploid tumors. None of 16 patients without demonstrable remaining cancer in the operation specimen had local recurrence. The presence of lymph node metastases was the most important prognostic factor.

DNA-Measurements on Formalin-fixed, Paraffin-embedded Squamous Cell Carcinomas from different ENT-Regions

DNA measurements were performed on formalin-fixed, paraffin-embedded squamous cell carcinomas, using the method of Hedley et al. Ultrasonication was sometimes necessary after enzymatic disintegration to dispose of residual cytoplasm. The isolated nuclei were stained with Hoechst 33258. DNA measurements were performed using a rapid system for static fluorometry (FLUORA-programme). The method proved to be highly accurate. The mean CV of the stem cell peaks from different tumours was 5.3. There was no difference between material less or more than 5 years old (mean CVs 5.2 and 5.5 respectively). RNase treatment had no effect and was therefore not considered necessary. The proliferative activity was calculated by computer assuming a rectilinear distribution of S-phase cells. Because routinely paraffin-embedded material can be used, DNA analysis can be performed on tumour material where the clinical outcome is known, in order to evaluate certain DNA variables.