Abstracts/Lung Cancer I2 (199s) 265-329

Genetic susceptibility to lung cancer witb special emphasis on CYPlAl and GSTMl: A study on host factors in relation to age at onset, gender and histological cancer types Alcxandric A-K, Sundberg MI, Seidegerd J, Tomling G, Rannug A. Deparbnenr o/ Toxicologx Nail InsliIute Occupational Health, S&a. Carcinogcnesis 1994;15:1785-90.

Genetically based differences in metabolism, related to Mspl restriction site and UC-Val polymorphisms of the cytochmmc P450 (CYP) 1Al gcnc and the null genotype of glutathione transferasc class mu (GSTMI), have been reported to be associated with lung cancer susceptibility. The present study was set up to establish the frequencies of the polymorphic genotypes of CYPIAl and GSTMI in Sweden, to evaluate a possible increased incidence of the genotypes associated with higher lung cancer risks among Swedish lung cancer patients and to try to make a combined risk estimate for carriers of multiple risk alleles. In a healthy control group, all under 66 years of age, 53% (174/ 329) of the subjects were of the GSTMI(-) genotype, while in a hospital control group 49% (39ff9) carried the GSTMI(-) genotype. In the investigated lung cancer patients this genotype was found in 56% (1651296) and among those patients diagnosed before 66 years of age the deficient genotype was found in 60% (78031). The highest proportion of the GSTMl(-) genotype was found in patients diagnosed with adenocarcinoma (63%. 29/46) and small cell carcinoma (72%, 21/29) before 66 years of age and among female squamous cell carcinoma patients (79%, 15119). The allelic variants in CYPIAI were equally distributed in lung cancer patients and controls. The ml/m2 and m2/m2 genotypes of the Mspl site and the IIc/Val genotype were, however, stightly over-represented in squamous cell carcinoma patients. Among patients with squamous cell carcinoma diagnosed before 66 years of age the ml/m2 genotype was found in 28% (10/36), whereas the same genotype was observed in 16% (52/329) of healthy control subjects A combined risk of squamous cell carcinoma was indicated for patients, diagnosed before 66 years of age, carrying both GSTMl(- ) and m2 alleles (OR = 3.0,95% CI = I .2-7.2).

Transient stabilization of p53 in non-amail cell lung carcinoma culturea arrested for gtowtb by retinoic acid Maxwell SA, Mukhopadhyay T . Dep~. Thoracic/Cardiovasc. Surgery Box 109, UTM.D. Anderson Cancer Cenkq ISlS Holcombe. Housron, TX 77030. Exp Cell Res 1994;214:67-74.

Proliferation of tive non-small cell lung carcinoma (NSCLC) culhrres was inhibited a&r 16 h exposure to retinoic acid. WC investigated whether expression of the ~53 protein correlated with the growth pattern of NSCLC lines observed in the presence of retinoic acid. Levels of wild-type ~53 protein underwent tivefold increases in lines H46Oa and H226b after 16 to 48 h treatment with 5 iM r&in&c acid but then decreased to undetectable amounts in these cell lines at&x 72 h retinoic acid treatment. Levels of ~53 transcripts remained unchanged during the time of incrcascs in protein expression in retinoic acid-treated H460a cells, suggesting that a post-translational mechanism was involved in the increased expression of the protein. Pulse-chase analysis demonstrated that wild-type ~53 was significantly more stabile in H460a cells treated with rctinoic acid, exhibitmg a half-life greater than 6 h, in contrast to 3 h for the protein in untreated control cells. The rctinoic acid-mediated effect was specific for wild- type ~53, since exprcssmn of mutant pS3 in the H596b and H322j cctl lines remained relatively unchanged even at&r 72 h exposure to retinoic acid. We conclude that rctinme acid induces stabilization of wild-type ~53 in NSCLC cells by a post-translational mechanism. Furthermore, increases in expression of ~53 were not responsible for the retinoic acid-induced transient inhibition of growth of NSCLC cells, since the growth of H358 p53-null cells also was inhibited by retmow acid.

Pathology

Distribution pattern of tbe bauunent membrane components is one of the Jignificant pmgnostic correlates in peripheral lung adenocarcino- mas Matsui K, Kitegawa M, Sugiyama S, Yamamoto K. First Department ojpolll~l~gy. Faorlly ofMedicine. Toyamo Med.~hmmaceuticof Univ. 263Osugilani. TOYOTA 93001. Hum Pathot 1995;26:186-94.

Clinicopathological variables that might have an effect 0” prognosis wcrc analyzed in 98 samples of resectable peripheral lung adenocarcinoma. Pathological

stage (stage 1 v stage II, III, or Iv; P < ,001). degree of central librosis (grade I or 2 v grade 3 or 4; P < .O l), and histological grade (well differentiated v moderately or poorly differentiated; P < .05) were shown to be prognostic factors, whereas any other variable, including patient age at diagnosis, sex, cigarette smoking habits, and tumor histological subtype and cytological type, showed no meaningful correlation with patient length of survival. The distribution pattern of the basement membranes (BMs) was significantly associated with pathological stage (intact v disrupted or abscnS P < .OOI). It was noteworthy that in stage I samples a signiticant relationship between the distribution pattern of the BMs and patient length of survival was found (intact v disrupted or absent, P < .oOl), although such a relationship could not bc detected when anal+ in samples from the other pathological stages. The distribution pattern of the BMs also was correlated with the presence or absence of lymph node metastasis but not with its extension. There were no meaningful relationships between the distribution pattern of the BMs and any other clinicopathological variables, including degree of central fibrosis, histological grade, etc. The distribution pattern of the BMs in peripheral lung adenocarcinomas might lx useful for postoperative therapeutic strategy and could serve as an important prognostic indicator for stage I lesions.

Clinical study of primary lung cancer with sarcomatous components Daido K, Arita K, Ejima T, Satoh R, Fujiwara M, Nambu S. Depertmenf of Respirakwy Disease, Hiroshima Red Cross Hospital, Hiroshima. Lung Cancer (Japan) 1994;34:1017-22.

The authors reviewed the clinical aspects of 5 patie@ of primary lung cancer with sarcomatow components (sarcomatous carcinoma) treated from 1988 to 1993. The median age was 60.2 years, 2 patients were male and 3 were female. Concerning the epithelial pattern, there were squamous cell carcinoma in 2 cases, and adenocarcinoma, adenosquamous cell carcinoma and large cell carcinoma in 1 case respectively. All cases underwent lobcctomy, and 3 cases had postoperative radiation therapy. Two patients lived long periods without disease. Radiation therapy was judged effective for local control of the disease Sarcomatous carcinoma seemed to be a clinically distinctive discasc in primary lung ca”ox

Cytologic characterization of bronchinl epithelial changes in small cell carcinoma of the lung Boucher LD, Yoneda K. Pafholo&Lsb. Medicine Service. Veterans AQoirs Medical Center: 2250 Leestown Road, Lexington. KY 40511-1093. Acta Cytol 1995;39:69-72.

Cytologic specimens obtained by fiberoptic bronchoscopy were examined in 111 cases; the diagnosis of small cell carcinoma of the lung was established with

this procxdurc. The findings ofcytologic examination were compared to those of histologjc examination of the biopsy specimens obtained simultaneously. Our aim was to evaluate other cell components in the specimen besides small cell carcinoma. The majority ofthe cases showed morphologic changes in the bronchial cpithelium, which ranged fmm benign squamous mctaplasia (59%) to atypical squamous metaplasia (8%) and squamous cell carcinoma (8%). In 6% of cases a large cell carcinoma component was found in addition ta the small cell carcinoma. The lindings show a good correlation with those of histologic examination of the biopsy specimens, indicating that cytologic examination is an excellent procedure for detecting concomitant changes in the bronchial epithclium in the setting of small cell carcinoma of the lung.

Cytologic features of peripheral squamous cell carcinoma of the lung Kamiya M, Uci Y, Shimosato Y. Clinical Laboratory Division. National Cancer

Center Hospital, I-I J-chome. Chuo-kw Tokyo. Acta Cytol 1995;39:61-8. Cytologic features of 32 peripheral squamous cell carcmomas of the lung

were rcwewcd. Fine nccdlc aspiration biopsy and curettage showed most of the tumor cells to be arranged in wrcgular cell fragments consisting of relatively small cells with scanty cytoplasm. They possessed mund to oval nuclei with coarsely granular chromatin, and some had large, prominent nucleoli Keratinizatmn was usually observed in small numbers of scattered cells, and a nuclear streaming arrangement was noted m some areas. When both keratinizatmn and streaming arrangements were absent. correct subtyping was impossible (12 cases). These cy?ologic fcaturcs were different from those of 3 t hilar squamous cell carcinomas studied as controls; there many carcinoma cells showed kcratmization, and small carcinoma cells were Infrequent. However. in all cases, sputum cytology was correctly interpreted because squamous dtffcrentiation was easily rccognlzed.