1
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

Monoclonal antibody MON-114: Detection of a marker for neuroendocrine differentiation in human lung cancer

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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