7
腎腕腓腉 臱腸腹腧腻腴膁膒膜臆臎 Vol. 33, pp. 529535, 2005 腝腔腠腋腊腎腕腡腚腗腅腄 EGFR 腓腞腙腢腒腈腟腇腀 腌腐腉腍腏腑腁腜腘腂腃腡腛腖腆 1 腃腙 腄腅 腒腋 1 腉腦 腠腖 腙腦 腂腈 2 腘腇 腟腥 1 腆腆 腐腌 腝腎 腚腨 1 腃腐 腂腔 1 臛臈 腑腢腪腍 1 腛腑 腤腐 腔腊 1 腝腔 腆腇 1 腐腥 腇腩 腒腅 1 腗腍腨 腝腠腧 3 腞腡 腏腩 腕腧 腆腞 1 腆腎 腚腨 腂腈 2 : 17 11 21 79 臂腖臞臫臹膪腳腒腥臒臻腕膅腋腏腎腨膄臭腖膮臵臫膆 膈腓膉腃腨膄腕腘腚腦臫腕自腖臟膮臵膈腥腛腏臰臀腖腏腛腪腩腳腮腀腯腴膆膤膠臉膺 腡腐腦腋腀腻 EBUS-GS腂臯膱腥臊膻腋腏腮膈臺臦臝膲腒腗臸膡腓臩腊腢腟腢腏臺臦腞腠 genomic DNA 腥臁臓腋腰腩腺腫腲腮腀腬腻腯腕腑膀臈膖臲腥腋腏腓腉腣 EGFR 臈腖 exon21 missense mutation L858R腛腏腕腗腭腶腨腱腵腷腆臼 膹腋腫腁腄腞腘腖臘臟腥腛腏膾膗臊膻腋腏 EBUS-GS 腗膞臑腕腞腠臠腔腂 腲腊EGFR 膵腖膱臄腆膑腓腔腠膾膸腊腟腕腗臐腕腜腇腈腫腖腊腍腡腉腓腆膣腊腢腡腊腀腔腇 膤膠臉膺腡腐腦腋腀腻臸膡EGFR腭腶腨腱腵腷 腨膁腮腶腖膛腕腗腈腖臊致腒膤膠臉 膫膎臅膓臃膭膤膠臉臯膱腆膻腤腢腑腂 腋腅腋臍膎腒腗腮腶腖腼腖膛腕膶膘腆腁 臺臦臩腚腒臌腟腔腂臤腜腁腡腉腖腞腃腔 腋腑腉腢腚腒腗腞腠臧臖腖腁腡膪膺膫 臯膱腝膙膪臯膱腆膻腤腢腑腂腏膾膗腤腢腤 腢腗腪腩腳腮腀腯腴膆膤膠臉膺腡腐腦腋腀腻 EBUS-GS腂腡腉腓腕腞腠膞臑腕腞腠臠腔腂 腲腊腅腐臮膛腔腮腶腳腼腒臯膱腥臊膻腌腡腉腓 腆腒腇腏腊腟腕腎腖膸 EGFR 臈腖 exon21 mis- sense mutation L858R腭腶腨腱腵腷腆臼 膹腋腏膃腥膭膳腋腏腖腒膽腌腡: 79 臞臫: 臹膪腳腒腧腳腒腂腑腖: 腆腾膡腒臋腆膮膡腒臋腃腁腖: 膥腌腙腇腉腓腔腋腏腄腖: 腘腈腖: 膄臔腔腋膧膊腔腋腅腒腖: 2005 1 膯臜臚腞腠臹膪腳腒腆臙膵腎腖膸腧腳腒腃腞腃腕腔腠臏腌腡腏腛6 膯腕膅臕臩腋膪腺腻腲腭腻腥臊膻腎腨膄臭腖膮臵臫膆膈腓膉腃腨膄腕腘腚腦臫腕臟膮 臵臫膆膈腥腛腏腏腛臰臀膊膃腔腕腑 2005 1 臱腸腹腧腻腴膁膒膒膜膷膨膢膟臷臤2 臱腸腹腧腻腴膁膒膚膒膜膷膨膢膚膒3 臱腸腹腧腻腴膁膒腋腮膈529 23

EGFR ˘ˇˆ˙˝˛˚˜ !# 1 - 聖マリアンナ医科大学 医学会igakukai.marianna-u.ac.jp/idaishi/www/336/04-33-6Inoue...EGFR ˘ˇˆ˙˝˛˚˜ !"# 1 $ 2 1 1 ˘ˇ 1 ˆ 1 ˙ ˝

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Page 1: EGFR ˘ˇˆ˙˝˛˚˜ !# 1 - 聖マリアンナ医科大学 医学会igakukai.marianna-u.ac.jp/idaishi/www/336/04-33-6Inoue...EGFR ˘ˇˆ˙˝˛˚˜ !"# 1 $ 2 1 1 ˘ˇ 1 ˆ 1 ˙ ˝

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Page 2: EGFR ˘ˇˆ˙˝˛˚˜ !# 1 - 聖マリアンナ医科大学 医学会igakukai.marianna-u.ac.jp/idaishi/www/336/04-33-6Inoue...EGFR ˘ˇˆ˙˝˛˚˜ !"# 1 $ 2 1 1 ˘ˇ 1 ˆ 1 ˙ ˝

� 6� 27������������: � 149.2 cm� � 41.5 kg� ��36.2�C� �� 70������ ���� 16 ���� ��114�70 mmHg� ����� ��� !�"� #$%&'��"� #(%&)*�"� +,-./01234� 56��7�� 897�"� :7;� <=>97?@� A6BCDE�"� FGHIJ�"�KLMNBCDE�"������� �Table 1�: OP� LDH 400 IU�l�ALP 525 IU�l �QR"ST� UVW KL-6 X25000 U�ml �Y�WQR� JZ[ \ P CY-FRA 43.9 ng�ml� SLX 184 U�ml� CEA 19.4 ng�ml�T4]^_`O?�������: 56 Xabc �Fig. 1�OP� de8fWghi�H%0j�kl8fWmnopWq%0jrs�tu� 56 CT �Fig. 2�OP� d S6vwW5&x�ryzi�{HJ|p}j�kl8fWmnopWs�Hq~�}jrtu�A6 CTOP� �d�Ws�p��rtu� �6 CTOP� ���W�� 6 mm�H��p��rtu� ��.�OP� F���� 5�� � 3� 5

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Table 1. Laboratory Data

Fig. 1. Chest radiograph on admission showed irregu-

lar-shaped mass lesion in the right middle lung

field and multiple small nodular shadows in

bilateral lung fields.

Fig. 2. Chest CT scan on admission showed irregu-

lar-shaped mass lesion with pleural indentation

in the right S6 and multiple small nodular

shadows in bilateral lung fields.

©Qª« ¬­®¯ V530

24

Page 3: EGFR ˘ˇˆ˙˝˛˚˜ !# 1 - 聖マリアンナ医科大学 医学会igakukai.marianna-u.ac.jp/idaishi/www/336/04-33-6Inoue...EGFR ˘ˇˆ˙˝˛˚˜ !"# 1 $ 2 1 1 ˘ˇ 1 ˆ 1 ˙ ˝

�������� ��������� ��EBUS ����� ����������������� ����������� �!��Fig. 3A�� "�� ����� #��$�%&'()����� �** !+����,�-.� /0$1��2���������� 3 456�7�!4�� ����������5�89:0���;��<� �Fig. 3B�� �0���=>�?���@*A=>�B �� ��CD��� EE�F0��G+H��G+IFJ�����K���5���=�L5��M�N����Fig. 4�� O�� AP�!QR5 genomic DNA

�ST�� UV'W)X�YZ["� EGFR 0exon18�19�21 �\!]#?^_��[`�a�

abcde�f$����� exon21 � heterozy-gous missense mutation �L858R����� �Fig. 5��gL� ]#?^_�\!�%h0i)jkl�]#?^_mn�d0o�� !+�o�&p'1011 p�� /0$� (q>r0st T4N3M1�stage IV�N�� uv� 7B)wJ��M�Lx+y*��z{|}M~���M~0+~,-*"��%�g !+�00� .��./LR���0�g��1g2�-�34��**�A�� 5�6�!O�� 30���Z)7$��+� %�8� 79���9��<� :4:�;��R+M:�<� (q�=�LR���>���5� ?�@�(q�h*"��A�B��� j��{��0CD�,���� ��� E�F�G¡Hy*� �;��I¢�<�F�� MS �Z{Z� [£�V¤0CD�Bg �� /0$� j��{��0CD�¥J�����y*,� 15K$��� ¦� XH§¨ �Fig. 6�LR�¦� CT© �Fig. 7����ª S60�L�EE«w�� M�N���O¬:���AP!�­B:�;�O�PQ�®¯�!�� /0$� y*,� 5Y°$�� CYFRA 12.5 ng�ml,SLX 87.6 U�ml� CEA 11.7 ng�ml�!�P�R±���!�� -A���CD�²S�³´�Tµ��+ �Fig. 8��

� �

uv� ���¶��2��U" �EBUS� ����V·W�N�1�� �X¸�Y0@Z0�[� ¹@N�2�� ºZ�\g�0�����]»0^¼3�� ³

Fig. 3B. The EBUS image revealed heterogeneous

internal echoes and an irregular margin of the

lesion, with almost no vessels or bronchi within

the lesion.

Fig. 3A. The EBUS image revealed that the probe was

adjacent to the lesion because of drainage

bronchus obstruction.

Fig. 4. Histological examination of the lung tissues

obtained from TBLB biopsy with HE staining

showed adenocarcinoma cells ��100��

j��{���P�����M0 18 531

25

Page 4: EGFR ˘ˇˆ˙˝˛˚˜ !# 1 - 聖マリアンナ医科大学 医学会igakukai.marianna-u.ac.jp/idaishi/www/336/04-33-6Inoue...EGFR ˘ˇˆ˙˝˛˚˜ !"# 1 $ 2 1 1 ˘ˇ 1 ˆ 1 ˙ ˝

����������� �3����������� ������������ EBUS � �!�"#�$� 1992%� Hurter �& 26'()� 19'(*+,&-.*/01234#���4�� 5�*$78�9:*�������;���<#�$� =>?@>AB&�����C1� 25D&�

=>?@>AB*$EF�+,G�H�IJ���KLMNOLPQRSTU����<#�$VW&/X� YZ[�7� CTN\]^���K_`�/�abc^���� da���Sefgh�SiH

Fig. 5. Missense mutations in exon 21 of EGFR.

Fig. 6. Chest radiograph at 15 days after commence-

ment of gefitinib.

Note improvement of the mass lesion in right

middle lung fields and multiple small nodular

shadows in bilateral lung fields.

Fig. 7. Chest CT scan at 15 days after commencement

of gefitinib.

Note improvement of mass lesion in the right S6

and multiple small nodular shadows in bilateral

lung fields.

jklm nopq �532

26

Page 5: EGFR ˘ˇˆ˙˝˛˚˜ !# 1 - 聖マリアンナ医科大学 医学会igakukai.marianna-u.ac.jp/idaishi/www/336/04-33-6Inoue...EGFR ˘ˇˆ˙˝˛˚˜ !"# 1 $ 2 1 1 ˘ˇ 1 ˆ 1 ˙ ˝

���� EBUS ������������ ����������������� ���������������� �!"� #�$%&'�()�*$�()+�,� -��./�0!"1��2�3+45��!��� 6789���� EBUS �EBUS-GS� 4:��;�<�����6789���2������=>9?�����@�A�B�=>9?��C�!DEF()��!���4� EBUS-GS ��=>9?���4GHIJ����K�6789��L��MM� N���B���()�O���2�3+��������-�()45��!��� B�PQ� �R-� 10 mmS'��T����� 76�+U�1�����3+4���+�V����5�� T-�B�1���=>9?4�� ������WX�within� �� 87� �Y������� ���!Z�[����WX �adjacent to� �� 42� �Y��� "\#�]������^��$%_`a4&b������� 3�MM()�cd+ adjacentto +!H� eH1���fg���� hijkl���&b����$%_`a�*'Tm�()���� 3�n)�eH adjacent to �- within���3+4eH1���Yg�3+��!4H�

��!1��o��+pq-E�� :*� rc�s+,�t-�uv.�A/0+��/O12v.34'�!A4�5���Y�� 2004�� Lynch -� EGFR �w>8xhy9z�K�]D�{6O�|4/O12v.3�A��Y�}~�w�?������7����3+��V��6�� 8-�e�+� ��.)9�Y�rc�,�t-u�R 275#�}~�w�?:�v.4c�E� 25 #4;���� ;�#�d� 9#� EGFR {6O���]3!��+3�� 8#� EGFR {6O�|�<��4� A(�,;�# 7 #��EGFR{6O�|�<�-E!���+�V����� 8-�M��3� EGFR{6O�|� EGFR4 EGF�=��eH�"���TE� BE4>"����?�������3+����]H� B�����}~�w�?�e���Q2�@�TE�3+������}~�w�?4;�2��6=��|�� EGFR4�����2� EGFR ��A������+�V����� 3E-�3+eH� }~�w�?4;���"\#�]���� 3��A���]3��3+4��TE�� A(� Paez -�,�t-�u�R 119#�B�� 61�� *"� 58����Ct-���� EGFR w>8xhy9z�K�{6O���c��+3�� EGFR {6O�|�Du� ��� *"�� ,��R�E��F"<�-E� B�EGFR {6O�|��QGH O�Y�+I¡��G@GH O��Y�+�V����7�� M�Lynch -� EGFR {6O�|� 119�,�t-�u�R���� 2 �- 25 � exon �����-¢�+3�� �|4 16Y��4BE-�J� 18�-21 �Y��+�V��]H� "\#�]���w>8xhy9z���K� exon18�19�21����EGFR {6O�����+3�� exon21 � het-erozygous missense mutation �L858R� 4<�-E�� 3� L858 �8£¤¥£¤¦§�-¨lM�©�ª�KLTE���«M!¬­®¯�Y�� B���� 3��K��|4 EGFR �°��'�!�±�7q���Y�d+pq-E�� SfeH� *"�����,��R��Y�"\#�}~�w�?�v.�Q4²/³N���+O���� P��}~�w�?�Q7��+3����� ´µ� Q75¶·R���4� ¸¹�ºS�Y��»�!�K�-�()�� »�!�T1��5���� U¼!v.��!4�� "\#�ed�$%

Fig. 8. Chest CT scan at 5 months after commencement

of gefitinib.

Note improvement of mass lesion in the right S6

and multiple small nodular shadows in bilateral

lung fields.

}~�w�?4�����Du� 1# 533

27

Page 6: EGFR ˘ˇˆ˙˝˛˚˜ !# 1 - 聖マリアンナ医科大学 医学会igakukai.marianna-u.ac.jp/idaishi/www/336/04-33-6Inoue...EGFR ˘ˇˆ˙˝˛˚˜ !"# 1 $ 2 1 1 ˘ˇ 1 ˆ 1 ˙ ˝

���������� � ������������� within�������� adjacent to ����� �!"#$� %&'(�)*+,�-./+� 012!�� EBUS-GS 3 45�#$6789� EGFR :;� <�=>-7$�0?@*� AB�,CDE:F@GH-�IJ@+�

� �

1� Kurimoto N, Murayama M, Yosioka S, Nishi-saka T, Inai K and Dohi K. Assessment of the

usefulness of endobronchial tumor invasion.

Chest 1999; 5: 1500�1506.2� Barry B. Goldberg, Robert M. Steiner, Ji-BinLiu, Daniel A. Merton, Glenn Articolo,

John R. Cohn, Jonathan Gottlieb, Barbara L.

McComb and Paul W. Spirn. US-assisted bron-

choscopy with use of miniature transducer-

containing catheters. Radiology 1994; 190: 233�237.

3� Okamoto H, Watanabe K, Nagatomo A, Kuni-kane H, Aono H, Yamagata T and Kase M.

Endobronchial Ultrasonography for mediasti-

nal and hilar lymphnode metastases of lung can-

cer. Chest 2002; 121: 1498�1506.

4� Hurter TH and Hanrath P. Endobronchial

sonography. feasibility and preliminary results.

Thorax. 1992; 47: 565�567.5� KLMN� OPQN*� RSTUV�&'�WX���YZ[\]'^3�_�`� ���a 2005; 27: 290�295.

6� Thomas J. Lynch, Daphne W. Bell, Ra#aellaSordella, Sarada Gurubhagavatula, Ross A.

Okimoto, Brian W. Brannigan, Patricia L. Har-

ris, Sara M. Haserlat, Je#reyG. Supko, Frank

G. Haluska, David N. Louis, David C. Christi-

ani, Je# Settleman and Daniel A. Haber. Acti-

vating mutations in the epidermal growth factor

receptor underlying responsiveness of non-

small-cell lung cancer to gefitinib. N Engl J Med

2004; 350: 2129�2139.7� J. Guillermo Paez, Pasi A. Janne, Je#rey C. Lee,Sean Tracy, Heidi Greulich, Stacey Gabriel,

Paula Herman, Frederic J. Kaye, Neal Linde-

man, Titus J. Boggon, Katsuhiko Naoki, Hide-

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thewMeyerson. EGFRmutation in lung cancer:

correlation with clinical response to gefitinib

therapy. Science 2004; 304: 1497�1500�

bcde KLMN *534

28

Page 7: EGFR ˘ˇˆ˙˝˛˚˜ !# 1 - 聖マリアンナ医科大学 医学会igakukai.marianna-u.ac.jp/idaishi/www/336/04-33-6Inoue...EGFR ˘ˇˆ˙˝˛˚˜ !"# 1 $ 2 1 1 ˘ˇ 1 ˆ 1 ˙ ˝

Abstract

A Case of Pulmonary adenocarcinoma with EGFR Mutation Diagnosed

by Endobronchial Ultrasonography with Guide Sheath

�EBUS-GS� Successfully Treated with Gefitinib.

Takeo Inoue1, Noriaki Kurimoto2, Miho Nakamura1, Masahiro Ohsige1,

Atsuko Ishida1, Junko Sagi1, Yoshitugu Fujita1, Yuka Matsuoka1,

Taeko Shirakawa1, Mamoru Tadokoro3, Teruomi Miyazawa1,

and Hiroaki Osada.2

A 79-year-old Japanese woman with no smoking habit was referred to our hospital complaining of

anterior chest pain. Chest CT showed a mass in the right middle lobe and multiple pulmonary nodules in

both lungs. For further examination, we performed transbronchial lung biopsy using endobronchial

ultrasonography with a guide sheath �EBUS-GS�� Biopsy specimens of the lung revealed adenocarcinoma,and she was diagnosed as lung cancer with multiple pulmonary metastases. We searched for the EGFR gene

mutations in one of the primary tumor specimens, and an exon 21 missense mutation �L858R� was detected.Subsequently, we initiated gefitinib, and it acted dramatically on both primary tumor and pulmonary

metastases. Since EGFR gene analysis needed a fair amount of tumor cells, it has been mainly analyzed by

surgically resected specimens. However, as EBUS-GS makes it possible to obtain biopsy specimens at better

site, it is expected that EGFR gene analysis will be performed with less invasive method using EBUS-GS.

1 Division of Respiratory and Infectious Disease, Department of Internal Medicine, St. Marianna University School

of Medicine

2 Department of Chest Surgery, St. Marianna University School of Medicine

3 Department of Diagnostic Pathology, St. Marianna University School of Medicine

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