339

Overexpression of P-glycoprotein in human lung carcinoma xenografts after fractionated irradiation in viva Mattem J, Efferth T, Volm M. German Cancer Research Center, Institute of Experimental Pathology, Im Neuenheimer F&l 280, D-6900 Heidelberg. Radiat Res 1991;127:335-8.

In viva exposure of a human epidermoid lung carcinoma xenogmft

to seven irradiation treatments of 10 Gy in coosecutive passages resulted

in expression of resistance to vincristine. This about threefold dmg

resistance was detectable with a single dose of 1 mg/kg viocristioe.

Characterization of the radiation-pretreated subline showed that

overexpressionofP-glycoprotein,asdeterminedhyimmunofluorescence

and Mabs C219 and 265/F4, occurred in this tumor. After six X-ray

fractions, only single positive cells were observed, whereas seven

fractions produced ao intense immuoofluorescent reaction with both

antibodies. Southern blot analyses indicated that no gene amplification

had occurred. This result shows that irradiation can influence expression

of P-glycoprotein and in thrs way influences drug resistance.

Pathology

Monoclonal antibodies in the detection of bone marrow metastases in small cell lung cancer Skov BG, Hirsch FR, Bobrow L. Dept. Pathology and Oncology, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen. Br J Cancer

1992;65:593-6.

Usmg conventional examination (CE) of H and E stained shdes from

bone marrow aspirates, m&stases can be detected in approximately

25 % of patients with small cell lung cancer. We investigated a panel of

monoclonal antibodies usmg immunohistochemistry in the diagnosisof

bone marrow infiltration from SCLC and compared the results with CE.

Seven monoclonal antibodies raised against epithelial antigens (CAM

5.2, MOV 15. NCCST 433, PE 35, LCAliL38, HMFG I and HMFG

2) were applied on bone marrow sections from three groups of pattents

(pls); (1) 19 pts m whom SCLC-m&stases were detected by CE, (2) 44

pts wth SCLC in whom m&as&es could not bedetected by CE, and (3)

20 pls with non-malignant bone marrow diseases. All the antIbodies

except LCA 1 /L38wercpositwein 60-90% oftheshdeswith intiltratmg

tumourcells ingroup 1. No posuive tumourcellsweredetected mgroup

2. A few plasma cells and megakaryocytes were slightly positive for

MOV 15 and NCCST 433, but no other positwe cells were detected in

group 3. In conclusion, the monoclonal antIbodies used in this study

may be us&l for diagnostvz purposes when a suspicious looking

mfiltrat~on is detected by CE. However, these antibodIes could not

detect metastatac tumour cells m the bone marrow s&ions from pataents

m whom CE did not reveal any turnour cells.

Monoclonal antibody MON-114: Detection of a marker for neuroendocrine differentiation in human lung cancer Van Duljnhoven HLP. Moors EHM, Groeneveld A, Timmer EDJ, De

Lcljb LFMH, Wagenaar SS et al. Molecular Oncology Section, Deprrrtnre~r of Biochemistry, Clniversiry of Nijmegen. PO Box 9101,

6500 HB Nijmgen. Cancer Latt 1992;63: 61-6.

Mouse monoclonal antibody MON-114 was generated upon

mumuwation with a human small cell lung carcinomacell line GLC-19.

lmmunohistochemicalanalysisofnormal tissueswithMON-I 14showed

stainrng of the adrenal gland, brain and peripheral nerves. With respect

to human lung carcinomas, 7 out of 8 small cell lung carcinomas were

positively stamed as well as 5 out of 5 carcinoid tumors, whereas only

4 out of 3 1 squamous cell carcmomas and 3 out of 19 adenocarcinomas

were weakly stained. Furthermore, 1 large cell carcinoma was negative

for MON.114 staining. Apparently, MON-I 14 stains cells of

naunxndocrme dlfferentlatmn.

Peripheral biphasic adenocarcinoma of the lung: Light microscopic and immunohiitochemical findings Cagle PT, Alpert LC, Carmona PA. Department of Pathology, Baylor College of Medicine. One Baylor Plaza, Houston, 7x 77030. Hum

Pathol 1992;23: 197-200.

We report hw cases of peripheral hiphasic adenocarcinoma primary

in the lung. To out knowledge, peripheral adenocarcinoma of the lung

with a spindle- cell component has not been described previously.

Diffuse positive cytokeratin and negative vimeotin immunostaming of

the spindle-cell components support an epithelial differentiation of the

malignant spindle cells. Although study of additional cases is neated,

our initial findings suggest that immunohistochemical staining pattern

may help distingmsh these neoplasms from other biphasic neoplasms

primary or secondary to the lung, such as carcinosarcoma or malignant

mesothehoma.

Neuroendocrine phenotype in lung cancers: Comparison of immonohistochemistry with biochemical determination of enolase

isoenzymes

Brambilla E, Veale D, Mom D, Morel F, Dubois F, Brambilla C.

Service d’Anatomopathogie, Hopital Michallon, CHURC. BP 217X, 38043 Grenoble Ceder. Am J Clin Pathol 1992;98:88-97.

The authors evaluated methods of recognition of neuroendocrine

differen&xtion in lung caocer because this is thought to bear prognostic value. One hundred forty lung tumors were divided by

immunolustochemical analysis using neuroendocrine markers (neuron-

specific enolase, Leu7, chromogranin, neural cell adhesion molecules,

SLllIl4, and Leul9) into two groups of 51 neuroendocrine tumors

positive for three neuroeodocrine markers and 89 non-neuroendoaine

tumors. Biochemical determination of en&se activity and &enzyme

distribution showed that the level of total en&se activity was similar

between neuroendcaine and non-neuroendocrine tumors. 6gamma and

gammagamma enolase &enzyme percentages were higher in

neuroendocrine tumors. A cut-offof gamma enolase 46 (t)gammal?l +

gammagamma)at 14% gaveasensitivity r&of 84% andspecificity rate

of 97 96 in separating neuroendocrine and non- neuroendocrine tumors,

whereas immunohistochemical analysis usmg am-gamma enolase had

low specificity (68%) and immunohistochemical analysis with Leu 7

and chromogranin had high specificity (97%) and low sensitivity (37%

and 60%) levels for neuroendocrine tumors. The best prediction of

neuroendocrinedifferentiationwasobtained using immunohistochamical

analysisagainst neural cell adhesion moladescombined with biwhermcal

estimation of en&se using gamma enolase of 14 96 and a gammagamma

isoenzyme more than 3 I.

Correlation behveen nucleolar organizer regions visualized by silver staining and the growth rate in lung adenocarcinoma Ogura S, Abe S, Sukoh N, Kunikane H, Nakajima I, Inoue K et al. First Department of Medicine, School of Medicine, Hokkaido University, Nishi 7-chome, Kita IS-JO, Kita-ku, Sapporo 060. Cancer 1992;70:63- 8.

Background. The value of nucleolar organizer regions (NOR)

visualized bysilverstaining(AgNOR) for thehistologic differentiation,

pathologic staging, and estimation of growth rate was assessed by the

mvestigation of paraffin sections from 58 lung adamcarcinomas.

AgNOR consist of NOR- assoaated proteins, and the numba of

AgNOR might be related to proliferative actiwty. Methods. In lung

adenocarcinoma, the growth rate can be measured by means of chest

radiographs. Using this technique, thz authors studied the correlation

between the mean number of AgNOR and growth rate. Results. The

mean number of AgNOR ranged from 1.8 to 6.3 (mean + standard

deviation, 4.0 * 0.8). Neither the degree of histologic differentiation

nor the pathologic stagmg was related to the AgNOR count. The tumor growth rata was estimated on the bass of the doubling time in the chest

340

radiographs of 13 patients. The doubling time ranged from 80 to 760 days. There was a high inverse correlation between the AgNOR count and the doubling time (r = - 0.910; P < 0.001). Conclusions. Thus, it appears to be possible to use the mean number of AgNOR as an index of proliferative activity.

Detection of a novel markes in the bronchial secretions of patients with non-small cell lung cancer wing the 4B5 monodonal antibody Deutsch MA, Pence JC, Kerns B-JM, Plate CA, Kinney R, Gooch G et al. Duke University Medical Center, Box 3056. Durham. NC 27710. Cancer 1992;69: 2894-2904

A murine monoclonal antibody designated 4B5 was raised against the high molecular weight fraction of pooled sputum from patients with non-small cell hmg cancer (NSCLC). Immunohistochemical staining indicated that 4B5 binds to histologically normal bronchial epithelium distant from tumor in 72% (39 of 54) of patients with NSCLC, but it bids to the primary cancer in only 13 96 (7 of 54) of the same patients. The antibody reacted less intensely with the bronchial epithelium in 16.6% (3 of 18) of autopsied patients without significant lung disease. The antigen recognized by 4B5 is a high molecular weight glycoprotein of more than 400 kilodaltons, judged by gel filtration and sodium dodccyl sulfate-polyacrylamide gel electrophoresis and western blot analysis. Antigenic activity persisted after heating and resisted treatment with neuraminidase, but it was destroyed using protease and periodate. Multiple epitopes were present on each molecule recognized by 4B5. The determinants recognized by this antibody deserve additional study as possible markers of premalignant change in patients with NSCLC.

Prognosticsignificanceofhistopathologicsubtypeandstageinsmall cell lung cancer Fraire AE, JohnsonEH,YesnerR, ZhangXB,SpjutHJ, GreenbergSD. DeparrmentojPathology, UniversiryojM~sachuetts, Medical Center, 55 Lake Ave N, Worcester, MA 01655. Hum Pathol 1992;23:520-8.

A study of 149 light microscopic tissue slides from 147 patients with recorded initial diagnoses of small cell lung cancer (SCLC) (114 cases) and undifferentiated carcinoma (35 cases) was undertaken to test the reproducibility and prognostic impact of a new histopathologic subclassification of SCLC proposed by the Pathology Panel of the International Association for the Study of Lung Cancer (IASLC). This study was further designed to test the impact of clinical stage, age, sex, and race on survival. The tissue slides were blindly reclassified as SCLC or non-SCLC by a panel of five pathologists with no knowledge of the initial diagnosis. The SCLCs were divided into the three subtypes outlined by the IASLC pathology panel: small (classic or pure), mixed (small cell/largecell), and combined (small cell/squamous carcinoma or small cellladenocarcinoma). Smallcell lung cancer wasclinically staged as local, regional, or distant. Consensus diagnosis (defined as agreement by at least three of the five pathologists) was achieved in 144 (96.6%) of the 149 cases. Of these 144cases. 124 were reclassified as SCLC (115 [92.8%] small, five [4.0%] mixed, and four [3.2%] combined) and 20 were classified as non-SCLC. The median lengths of survival for the small, mixed, and combined subtypes were 225, 1,110, and 203 days, respectively (P = ,025). Adequate staging data were available in 123 of the 124 SCLC cases. Of tbe 123 SCLC cases, 27 (21.9%) were local, 22 (17.9%) were regional, and 74 (60.2%) were distant stage. The median lengths of survival for the local, regional, and distant stages were 428.25 1, and 111 days, respectively. This association was highly significant (P = .COOl). We conclude that stage is the major determinant of survival in SCLC. Mixed subtypes had significantly longer survival times than the small or combined subtypes (P = ,025). Survival times were longer for women than for men, and the survival time difference between men and women was significant (P = .0028). We found no significant differences in survival according to age or race.

Clinical assessment

Postoperative increase in soluble interlwkin-2 receptor serum levels as predictor for early recurrence in non-small cell lung carcinoma Tisi E, Lissoni P, Aogeli M, Arrigoni C, Como E, Cassina E et al. Divisione di Chirurgia Toracica, Ospedak San Geardo, 20052 Monza, Milan. Cancer 1992;69:2458-62.

It is known that interleukin-2 (IL-2) plays an important role in the activation of host antitumor immune response. In addition to IL-2 cell surface receptor, a soluble form of IL-2 receptor (SIL-2R) may be released in the blopd and potentially be involved in the regulation of IL- 2 availability. High SIL-2R levels have been found in patients with lung cancer. The current study evaluated the influence of changes in SIL-2R serum levels during the periopcrative period on early relapse rate in patients with operable non- small cell lung cancer. The study included 60 patients (epidermoid carcinoma, 33; adenocarcinoma, 27). Serum levels of SIL-2R were measured with an enzyme immunoassay before surgery and 7 and 30 days after surgery. A surgery-induced increase in SIL-2R levels was seen 7 days after surgery in 38 of 60 patients. On the 30th day after surgery, SIL-2R values were lower than the preoperative values in 32 patients (Group A) or still greater in the other 28 patients (Group B). After a median follow-up of 10 months, relapse occurred in 19 of 60 patients. The relapse rate was significantly higher in Group B than in Group A patients (16 of 28 versus 3 of 32, respectively; P < 0.001). This differencealso was significant in relation to histotype and node status. This study shows that the persistence of increased SIL4R levels in the postoperative period is associated with a higher early relapse rate in patients with operable non-small cell lung cancer. The impact of SIL-2R levels on relapse suggests that host immune defenses may influence theclinical course ofpatients with lung cancer. Therefore, theevaluationofSIL-2Rin theperioperativeperiodmayrepresentanew prognostic biologic factor in operable non-small cell lung cancer.

Serum laminin PI in small cell lung cancer: A valuable indicator of distant metastasis? Nskano T, Iwahashi N, Maeda J, Hada T, Higashino K. 7&d Dept. Irtternal Med., Hyogo College of Medicine, l-l Mukogawn-rho, Nishinomivn, Hyogo 663. Br J Cancer 1992;65:608-12.

Serum laminin Pl was studied in patients with small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC) respiratory infections, pulmonary tibrosis, and in normal subjects. The level of serum laminin Pl was elevated (> 1.27 U ml’) in 58.9% of SCLC and in 11.5% of NSCLC patients. Median value in SCLC was significantly higher than that in NSCLC (P<O.Ol) respiratory infection (P<O.Ol), and in normal subjects (P<O.Ol), but not statistically different from that in pulmonary fibrosis. The levels of serum laminin Pl in SCLC were related to therapeutic response. However, no certain correlation was established between the level of laminin Pl and the clinical stage of SCLC.

Bronchoalveolar lavage in lung cancer Semenrato G, Poletti V. 1st di Med Clia dell Univdi P, Clinica Medico I, Vin Guistininni 2, I-35128Padova. Respiration 1992;59:Suppl l:44- 6.

The analysis of soluble and cellular components of bronchoalveolar lavage (BAL) fluids might help the diagnosis of a specific tumour. Up to now disease specific humoral constituents have not yet been found. Concerning cellular recovery, BAL can be useful particularly in patients with bronchiole-alveolar carcinoma. The overall diagnostic yield in the case series presently available in the literature ranges from 35 to 69%. We evaluated the usefulness of BAL in the diagnosis of diffuse neoplastic lung lesions. The BAL provided a diagnostic yield in 75.9%