st. marianna university school of...

10
臤腱腲腩腵腯腼膄致膋膺膿 Vol. 33, pp. 393402, 2005 腓腎腈腂腋腉腏腊腁腅腀腃腑腇腐腒腄腌腆腍 腑腉 腎腓 1 臓臨 腈腅腌腒 腐腖 腍腆 1 腋腌 腐腖 腔腊 2 腍腏腈腖 腑腓腕 1 : 17 9 16 膇腏臈腚膑腗腷臠WHO 腥膃grade IV膇臈腙臡臈臡腇膴膸腎腤 腟腙腖膓腌腥腤臈臡臣腘腓腂腔腚 膢膍臦臫膜膷腅腡腛 膁臣臦腇臒腄腢腥腔腂腤腇膼臣膥膕腘腡腣臶腫腴腀腵臦腙膩臄腇腍腓腓腁腤膥膕腕膆腟腻腂腔腋腥腢腙膂臦腙膊膤腨膮腒腑9 膇腏臈臭臙腘臈腱腀腪腀腙 glial fibrillary acidic protein 臈腱腀腪腀腙 laminin 腙膠 臌臩臚腨膮腂膗臕腳腀腬腀膦膘腨腂腔膎膹腍腑腇腨膗膧腎腤 膁臣膷 腚膤臍腌腥腗腆腒腑腜腑5 腙臈臭臙腆腢 microdissection 膆腣腊腔膉臊腍4 臇腙腱腀腪腀 D3S1284, D7S507, D10S226, D17S786腂腔 mi- crosatellite 膈臥腨膮腒腑3 膇腏臈腕腚腕臬腉腺腗腒腑 microsatellite in- stability 腞腢腥臫膜膷腨膽臁腎腤膡膅腖膭腄腢腥腑腇2 腕腚腘腙腝 microsatellite instability 腇腝腢腥 膁臣臦臏腍腗腂腖臸腌腥腑膳膉腙膤腆腢膇腏 臈腙臈臡腚臖腘腡腣膷腬腶腺腇腺腗腤膃臠腇臃膵腌腥腑腇腄腊腆 腷臠膇腏膗臕腳腀腬腀膦microdissection, microsatellite 腂腀腃腁 膇腏gliosarcoma: GS臈臡腖膏膟臡 腇膴膸腎腤臮臠腙臭臙腰腮腀腵腨臼腖腎腤腷 WHO 腥膃 1腕腚 膇臈 glioblas- toma: GB, grade IV腙腶膝腘腥膃腌腥腤GS 臣腚膙腞腔膑腕腐腙腠腆GB 2臬臲腙0.2膰腌腥腔腂腤 23GS 腚臅腘 GB 腕膞臡腌腥膟臡腍腣臙腘腝腢腥腤腽腚腂腏自腻腷臠自腻臠臭 臙膔臈膌膚腎腤 4῏ΐ7GS 臗腚 1895 Stroebe 8腇臐腞腔 腂腑腇臂腚腐腙臰膸腚膒膾腌腥腔腂腑腆腍1955 Feigin and Gross 93 GS 膰腍腋腙腟腧GB 腘臯臘腎腤臈膢膍腇 臈膁腍腑腟腙腕腁腦腃腖臝膹腍腑腐腙膩GS 腚膴膯臈腖腍腔臹腌腥臈臡腙膷腬腶 腨膈腎腤腑腞腘臟臱腉腙腟腻臭臙膋10῏ΐ13腠膷腬腕腹腂腑膥膕 1415腇膮腧腥腔腈腑GS 臣腘腓腂腔膧膸腜腕腘 4 腓腙臦腇 臒腌腥腔腂腤 16臵腽腚膨腃腂膢膍臦Feigin and Gross 9腸膩臱腉腙膰腇腗腌腥腔腂 1011Fig. 1a腗腅 膢膍臦腕腚臈臡 腚膢膍腌腜腶腺腎腤腖腍腔腂腑腇腐腙膩腙膥 膕腆腢膢膍臋腹膷臈腙臺腖膭腄腢腥腤腡腃 腘腗腒腑 1718GB 腇臛臎腍腑 臭臙腇臈膁腎腤腖腂腃腟腙腕腁腤腇 19Fig. 1b腋腙臦腚臞腆腢腥腔臣腎腤 GS 腨臦腕腈腏腢腨臠腘腍腂臵膻腚 臫膜膷1 臤腱腲腩腵腯腼膄致膋 臜臸腟腻2 腽腟腾膐膬 臧至腼腭腵腮腀 臔膤膶膄 393 37

Upload: others

Post on 26-Sep-2020

0 views

Category:

Documents


0 download

TRANSCRIPT

Page 1: St. Marianna University School of Medicineigakukai.marianna-u.ac.jp/idaishi/www/335/06-33-5Masatomo...rol 1974; 33: 456 471. 7 Barnard RO, Bradford TS and Thomas DGT. Gliomyosarcoma:

� � ��������� Vol. 33, pp. 393�402, 2005

��������� ��������

��

��

���

���1 ��

��

���

� �1 �

��

���

���2 ��

���

����

1

��� :� 17 9� 16��

� �� ��������� �WHO ��� grade IV� � �!�"��# ���$%&'()"*��+,(� ���"�-#./0� �123�� �4�3�� �567�3� 89:�;-3� $<=>,0/($� ?"�@-���AB#9CDEFG�3"H�I$�JK..L(� �AB M���@����N�O�/0P,>"Q3"�RS�OTUV� 9 "� �WX#���GYG" glial fibrillary acidic protein* ��GYG" laminin"Z[�\]^OT/� _`!aGbGc"dO�/0efKV$#g$O_�h'( �;-7�� �Si+,�jUV� kV� 5 "��WXj> microdissection ��%� �%� &��%O�l0mnK� 4o"�GYG �D3S1284, D7S507, D10S226, D17S786�O�/0 mi-crosatellite pqOTUV� 3 "� � ���%* �% rst�UV microsatellite in-stability $'u>,� �567�3� Ovw'(xy*z=>,V$� 2 � �%#"{microsatellite instability${>, �;-3� #(|K�/*)}+,V� ~m"S�j>� �" ����� #9C7�*+$t�(�,�$��+,V�

��������� � �� _`!aGbGc"d� microdissection, microsatellite

��

� � �gliosarcoma: GS� �����*�-���$%&'(���"WX��G�O.�*'(����� � WHO ��1� ��!� �glioblas-toma: GB, grade IV� "��#��+,(� GS "�-��u0� � �"/0� GB "1 2� ���r�"1 0.2*2�+,0/(2�3�� GS "������# GB ��+,� �-����3%WX#{>,(�4� ���� �� �����WX��� 3� �� � �� �� �5�#��'(4��7�� GS "6�� 1895# Stroebe8� $�u0�/V$� 7���"�&��8�+,0/V� K

jK� 1955� Feigin and Gross9� � 3 " GS O2�K� P"�9� �GB :#� '(��12$ �;KV)"� L¡¢*£fKV� �"H�GS �%¤��*K0'�+,� ���"7�*+Op;'(Vu#� ¥¦s"��WX��S�10��13�§7�<=O�/VAB14�15�$T¨,0©V�GS :" ��-#./0h&k # 4."3$

><+,0/(16�� ª��«?�� �123� Feigin and Gross

9� ¬H� ¦s"2�$�+,0/(10�11� �Fig. 1a�� �8 �123� �7�� ����12:@#*+'(*K0/V$� �"H"ABj>12­®7�$ �"A¯*z=>,(9¢#�UV17�18�� ª�� �4�3� GB $°±KV4�WX$ �;'(*/¢)" L($19� �Fig.1b�� P"3�4�j>B,0�-'( GS O3; ©²CD�#EK/� ª³� �567�3� �

1 �������� ´}���2 µF�¶·¸ ¹º�G»��G H¼S½

393

37

Page 2: St. Marianna University School of Medicineigakukai.marianna-u.ac.jp/idaishi/www/335/06-33-5Masatomo...rol 1974; 33: 456 471. 7 Barnard RO, Bradford TS and Thomas DGT. Gliomyosarcoma:

����������������� �� ������20�21� �Fig. 1c�� ��� GB ��������������� ���� ����� ����Fig. 1d�� ����� �� GB ���� !"#$%&' ��������(�)���*14�15�

�+,-.�� /.0��1 �23�� � �4��� � GS � 2���567)������ �bi-clonal tumor� ��89:� /����;< �=�>?��@A ��16�� B8� GS ��� �/���C6�� ?�� ����� � ������ GS � 1D������ �monoclonal tumor� �E�89:� �23�� F �4��� ��GHI����/.0���JKL�M�8NOPIQRS0�T�6-.8C)�10�11�� 17��19�� UV��W��PIXY�Z: GS�[\� monoclonal tumor���/���]�678C)� Boerman 022�� fluore-

scence in situ hybridization �FISH� � comparativegenomic hybridization �CGH� ���� GS ������������6^_`5a�b0.��*�)� -0�� Birnet 023�� GS �������?� p53cdW�5������ Reis024������� p53�b60e�?� PTEN�5F p16 �CDKN

2A�fg9ZhMDM2� CDK4��i��@A ��*�)�GS ���jk�-0�l�)m�� �XY��

9��� ���8 ����� � ����� ��no �p7)� qrPIo ��st�u^_��vwx y z!{���� ������"|�#},~�����o���b)� �W��PIo��� microdissection $������������%�� microsatellite �MS� ���8�� ���IM&�o �)�

�����

��1997�2004 '�K�����)��� 9 ��o

���)�L 7�� �L 2�� '( 35�73��)� 56.3 ��� ��-.)o`� 10 �������"���� 2�3*���� ������+,�� -.qr���)m��"� ¡��¢£¤��H&E� ^_��/¥¦§¨�^_17��p7)� 69� �XY�©"�ª�«¬�­P�01.®¯°� ±�²³´�cdW��XY�°�µ2�38p¶.)� 939·��

Fig. 1. Hypotheses for the histogenesis of gliosarcoma �GS�. a. Vascular theory. Sarcomacells �green� arise from vascular pericytes in glioblastoma �GB, red�. b. Meninxtheory. Sarcoma arises from mesenchymal cells that are transformed from

meningeal cells. c. Precursor cell theory. Both GB and sarcoma cells arise from a

common precursor cell. d. Metaplasia theory. GB cells undergo mesenchymal

metaplasia �yellow�� leading to the development of sarcoma.

¸¹ºl »¼½4 0394

38

Page 3: St. Marianna University School of Medicineigakukai.marianna-u.ac.jp/idaishi/www/335/06-33-5Masatomo...rol 1974; 33: 456 471. 7 Barnard RO, Bradford TS and Thomas DGT. Gliomyosarcoma:

�����������3 mm ��������� 0.3� � ����������� fibronectin ����������������� �0.1� trypsin, 37�C� 30 ���glial fibrillary acidic protein: GFAP, laminin, CD10�; proteinase K solution �Dako, Carpinteria,USA, !"�� #$� 5� �CD31�; 0.05� prote-

inase, 37�C� 15� �collagen IV��� %&���'�GFAP ()*+,-.�� �Dako, !"�� �laminin /0*+,-.�� �LAM-89, Novocas-tra, Newcastle, UK, 50�� � fibronectin ()*+,-.�� �Dako, 500�� � collagen IV /0*+,-.�� �CIV22, Dako, !"�� � CD10/0*+,-.�� �56C6, Novocastra, 100� 123� CD31 /0*+,-.�� �HM57, Novo-castra,200� ��4� 56��7 4�C8 169�:;<�� Phosphate-bu#ered saline �PBS� 8=��>?��4� peroxidase-polymer @A&���Envisionuniversal, Dako� 7#$8 30��:;<� diaminobenzidine BC��4D�E����� ���������������������� �0.1� trypsin,

37�C� 30��������� F�����GHD�GFAP ()*+,-.��7:;<� PBS �2I>?�� rhodamine JKL�MNO IgG ���Dako, 50� 7#$8 30 ��:;<�� &��P����� laminin/0*+,-.��QI4'� b-III tubulin /0*+,-.�� �Promega,Madison, USA, 2000� 7 4�C8 169�:;<PBS 8>?���� biotin JKL�RMS IgG

�� �Dako, 500� 123 fluorescein isothiocy-

anate �FITC�@A streptavidin �Dako,25�7#$8T 30 ��@A;<�� UVE�' TO-PRO-3iodide �Molecular Probes, Eugene, USA; 2 mM� ��4�25�� VE �'��W�X �Axiovert 200 M,Carl Zeiss, Jena, Germany� 8YZ�� 30�mW [.\�� 1�mW �])M^_`�� 5�mW a])M^_`���b��: 488�� 543�� 633�nm���cIde�f,g,hSi^�Dj�kl�����LSM510 Meta, Carl Zeiss��MS�����������mVE��4 microdissec-

tion �Leica Microsystems, Wetzlar, Germany� �D

�n�� �n�123�n�������� Pop�56� proteinase K bu#er �50 mM Tris-HCl, pH 8.0; 1 mM ethylene diamine tetraacetic

acid �EDTA�; 0.5� Tween 20; proteinase K �250 mg

�ml�� �8 55�C� 72 9����� q�%��!r7�D��s^t�uR, PCR ��4v DNA�"#����26�� &�� $po�w%�!r�4x� MS R,y, �D3S1284, D7S507, D10S226,D17S786

22�; Invitrogen, Frederick, USA� 123 b-

globin z&{� PCR ��4 �denature: 95�C� 1�� annealing: 52�C� 2�� extension: 72�C� 2��45 cycle; final extension: 72�C� 7��� DNA|%�12� ()[*).[}~�.�'��(�� �����M^8�.VE����� �(�'�(kl���M�[ �Kodak digital science 1D, ver. 2.0.2,New Haven, USA� ��4D)�*�+����

� �

����HEVE8'� vD��,�14D GB7�n�

-���������L,��.cI/01�56��.�� �Fig. 2a�� GB�'�234���5r��6�n��28�;o� 7����"w7%�8'���8�D4�� %9� �n�8':���2�"����8� ���n ¡����56¢n�;£���<�¤�D4�� =mVE8'� GB �8'�2-�2���>���¥�¦?��L,��¤����@�� �n�8'A6��2����§po� -¨�J��B©��ª��Fig. 2b���������n/«1��8QI GFAP27�' GS v,� GB��¬C��¤�� �nD:���2­��®'E¯�°�� �Fig. 3a�� �n��F±56²1³´��¯�BGHR,y,� laminin, fibronectin123 IVr collagen

19�28� 7��µ�2R,y,8QI CD1029� �VE����� Laminin, fibronec-tin 7 IVr collagen 'vD��BGH7:���n�2�C��¤���� ¶¨�VE��=mVE��nI´�L,��·¸AJ�� �Fig. 3b, c��CD10'�n�2�%���§C�8� =mVE�L,�7'%J��°���@¹ºK�� »�� ��L?R,y,� CD3130� �F±VE¸����� ��n�2�'v��®'§po�°�� �Fig. 3d��

��n��w¼½ 395

39

Page 4: St. Marianna University School of Medicineigakukai.marianna-u.ac.jp/idaishi/www/335/06-33-5Masatomo...rol 1974; 33: 456 471. 7 Barnard RO, Bradford TS and Thomas DGT. Gliomyosarcoma:

��������������� GFAP �rhodamine ��� ���

����� laminin �FITC ��� ���� ���� ��������������������� 9� GS�� GB �� !� ����� !� "#�$� GFAP � laminin ���%&'( �� )*#+,�� �Fig. 4�� +-�./�0���� GFAP �12������ b-

III tubulin31� ���� ��� �3��%&'

( �$45"#� 67�8�9$: "#��Fig. 5��MS ��GS 4;,* microdissection !����� ��

�-<=������>� ?��@ADNA�B50�� DNA ��C4���)!���! b-globin

D�E� PCR �����FG� 4� GS ���H#�@A,*IJ�KLM$�*#H� NOPQLRSTUV�DNA�W$X��Y+04Z,*[\0��]^_��� `a 5������� MS

Wb�]^� Fig. 6 !c&� d 1�����!D3S1284� D10S226�� ���! D7S507� D17S786�MS instability �MSI�$ )*#� d 2�����!�YD7S507�MSI$Y*#�� e��d 3�����!D17S786�MSI$fa� ���!�D3S1284�MSI�D7S507� LOH �loss ofheterozygosity� $ )*#�� d 4 �����!D7S507�MSI� D10S226�gh$fa� ��!� D3S1284, D7S507 � D10S226 � MSI $: "#�� d 5�4;!�����$ie#+,��$� D3S1284, D7S507, D10S226 ����������j� MS Nk�L�c0� D17S786 ����� MSI ��0����

GS � GB ���$lm&' n+@Ao,*pq3�r!�stu>� ��v���wxy!u��z{,*"|$+"#�t�10��13�� 19�� z#�!�GS �\$%v� �GB� �V$%v�����,*+'l}���~�*#� ���������%��!&'0 GB ��()0��w&'�"#���17�18�� 0,0� �*��Ew+��pq!<aGS� monoclonal tumor ���v�� GB f'�� GB �������!&'&'� ��,W$�eauuf'22��24�� ��0� ��w�� � ������ ��H#$�0��,���-.�� ���F���W.!�>����pq�����eH� GS !� GB ,*�%����&' ��w�� $��!�m&'�,�/�@A��!400�� ��� ��w�� � GB ������V�!��0� �3� n��������%&'� ���� ��)�� F#!¡¢t GFAP �laminin ���� ����� +-� £¤¥;1!<'40�� laminin �¦§US�¨©¥;� �fibronectin �ª«US�¨©¥;��2¬� !3­0���45Nk�L�c0�$ �Fig. 3b, c�� ��� !� GFAP �ª«US�¨©¥;� ��@Y}®¯$°5+ laminin ¥;�±²0�� 9 �GS �� GB �� �GFAP- rhodamine�� ����� �laminin- FITC� !� "#�$� �3���%&'( ����45"#+,���Fig. 4�� F�]^!��u�W³$°5�f'�eH´µ! ��w�� �¶a�~�'F�$�t'� ������ !·�¸� GB �����

Fig. 2. Histology of gliosarcoma. a. Bimorphic ap-

pearance of a gliosarcoma in which the uniform

spindle component is a fibrosarcoma �H& E��b. Reticulin stain. Reticulin invests individual

mesencymal cells, while the glial component is

devoid of reticulin. G, glial component. S, sar-

comatous component.

6¹�º »¼½7 *396

40

Page 5: St. Marianna University School of Medicineigakukai.marianna-u.ac.jp/idaishi/www/335/06-33-5Masatomo...rol 1974; 33: 456 471. 7 Barnard RO, Bradford TS and Thomas DGT. Gliomyosarcoma:

Fig. 3. Immunohistochemical characteristics of gliosarcoma. a. GFAP is strongly positive

in glial component, but negative in sarcomatous part. b, c. Lamin �b� andfibronectin �c� highlighted sarcomatous component, but were absent in glial area.d. No CD31 immunoreactivity is detected in gliosarcoma. Arrows indicate CD31-

positive veins. G, glial component. S, sarcomatous component.

Fig. 4. Double immunofluorescent staining of GFAP and laminin

in a gliosarcoma. a. Laminin �FITC�� b. GFAP �rhoda-mine�. c. Nuclei �TO-PRO-3�� d. Merged image. �600.

������� 397

41

Page 6: St. Marianna University School of Medicineigakukai.marianna-u.ac.jp/idaishi/www/335/06-33-5Masatomo...rol 1974; 33: 456 471. 7 Barnard RO, Bradford TS and Thomas DGT. Gliomyosarcoma:

��������� ������� ��������������� �� !"#�$%&' �( GS )*+,�-� �./�01��Fig. 1c�� 23� GB �(24GFAP 567�89���:;*<=� ��> ���?� *@

�ABCDE�FG� HI*JK- GB ��GFAP L"�MN��>OP3��Q ���R&���� Q ST� U� VWX?�YZF� [\]�A3^F� ��� �� _`�aE������� bc d>*� efghi �j*�kl

Fig. 5. Double immunofluorescent staining of GFAP and b-III

tubulin in a gliosarcoma. a. b-III tubulin �FITC�� b.

GFAP �rhodamine�� c. Nuclei �TO-PRO-3�� d. Mergedimage. Tumor cells co-expressing GFAP and b-III tubulin

were labeled in yellow. �600.

Fig. 6. Microsatellite analysis on genetic progression of gliosarcoma. N, non-tumoral brain. G,

glial component. S, sarcomatous component. �� microsatellite instability.

mnop qrst �398

42

Page 7: St. Marianna University School of Medicineigakukai.marianna-u.ac.jp/idaishi/www/335/06-33-5Masatomo...rol 1974; 33: 456 471. 7 Barnard RO, Bradford TS and Thomas DGT. Gliomyosarcoma:

��� ����� � ����� � �������������������������� � !�� MS "#�$�%�&'()��GS ��*���*���+�,-��� MS ��%�&�.�/ 01��2�345 �1�4bp� �6� ����7�� �8����8��9allele :;<�=>����?� �heterozygous��MSI �@ABCDE�FG�=H I� MS ��J�����KL9� M�N� ON� &PN� GB�?Q�*� �R���32�33�� *��STUVW��9�XYZ� =[�\]^_�`���� �a�����b�c�9%�&=H�de���IXY� *���=>X���fg� MSI ��h���� I�� �i�j� +�klm!�>�32�� !��GB\GS9=H�?��J��n 3�7� 10� 17opqr� MS BVsV22��"�Y"#�$X�� >t� Boerman�22��u*�DNA�"�YGS�MS"#�$XYt�� microdissection9*�v#�#wY MS xyVW��h����$z{�|RY9��� }% 1� 3� 49��*���*� ~&�� MSI \ LOH ����� �Fig.6�� �i�'b�� ����:�TUVW����� ����� ��Q�������>X��b(� }% 2 � 5 9��*� ��� 1 �)�MSI ��R��� �*� ���>�%�&=H��* *�J�Y��� ������*� GB��+���m!_���� ����� ,��>�������� ���� ��%�&�/9��*�v#�=>X� MSI xyVW���m!_Z�-J�� ��� ?�)� MS BVsV�"��,-�./�J���GS ����� +��z{�*�01� �

2�����9�>Q� ��34\5��34�6�>�� Z���������� !��J� }%��� ����� � ����� � ���������"�����

� �

GS ���+��#&01� ,7��� 8���� � GB ��*�9��: �¡ ������ ��R���� �*�v#�~&� ���� ��;����klJ��� '<>��� MS"#9Z=����� b�� GS 9��*v#�GB �� ����m!_Z>�9¢>�X�� �

��XY� GS ��*v#�}% I������=>���Z����� �?�=� �J� ?Q�*��"��,7�£R����

� �

$¤¥�~¦@'V§V¨A©�ª" «�� ¬7B� ¬­®�C��$�"D�¯° E±²FG³ �´���µ�� >t� ��?H�/¶�n94·I$01�¸¹¸�2005J 4º 15I� »K� t�Y+L���

� �

1� World Health Organization Classification ofTumours. Pathology and Genetics of Tumours

of the Nervous System 2000� IARC Press,Lyon: 4244.

2� The Committee of Brain Tumor Registry ofJapan. Report of brain tumor registry of Japan

�19691993�� 10th ed, suppl 2000: 192.3� Meis JM, Martz KL and Nelson JS. Mixedglioblastoma multiforme and sarcoma. A

clinicopathologic study of 26 radiation therapy

oncology group cases. Mod Pathol 1991; 67:

23422349.4� Ng HK and Poon WS. Gliosarcoma of theposterior fossa with features of a malignant

fibrous histiocytoma. Cancer 1990; 55: 11611165.

5� Banerjee AK, Sharma BS, Kak VK and

Ghatak NR. Gliosarcoma with cartilage for-

mation. Cancer 1989; 63: 518523.6� Mathews T and Moossy J. Gliomas containingbone and cartilage. J Neuoropathol Exp Neu-

rol 1974; 33: 456471.7� Barnard RO, Bradford TS and Thomas DGT.Gliomyosarcoma: report of a case of rhabdo-

myosarcoma arising in malignant glioma. Acta

Neuropathol �Berl� 1986; 69: 2327.8� Stroebe H. Uber entstehung und bau derhirngliome. Beitr Pathol Anat Allg Pathol

1895; 18: 405486.9� Feigin I and Gross SW. Sarcoma arising inglioblastoma of the brain. Am J Pathol 1955;

31: 633653.

��*�+�¼½ 399

43

Page 8: St. Marianna University School of Medicineigakukai.marianna-u.ac.jp/idaishi/www/335/06-33-5Masatomo...rol 1974; 33: 456 471. 7 Barnard RO, Bradford TS and Thomas DGT. Gliomyosarcoma:

10� Morantz RA, Feigin I and Ransoho# J. Clini-cal and pathological study of 24 cases of glio-

sarcoma. J Neurosurg 1976; 45: 398�408.11� Schi#er D, Giordana MT, So$etti R, TarenziL and Bertolotto A. On the nature of the so-

called monstrocellular sarcoma of the brain.

Neurosurgery 1980; 6: 391�397.12� Ho KL. Histogenesis of sarcomatous compo-nent of the gliosarcoma: an ultrastructual

study. Acta Neuropathol �Berl� 1990; 81: 178�188.

13� Horiguchi H, Hirose T, Kannuki S, NagahiroS and Sano T. Gliosarcoma: an immunohisto-

chemical, ultrastructual and fluorescence in

situ hybridization study. Pathol Int 1998; 48:

595�602.14� Jacobsen PF and Papadimitriou JM. Mesen-chymal di#erentiation of cell lines obtained

from human gliomas inoculated into nude

mice. Cancer 1989; 63: 682�692.15� Kobayashi H, Sakiyama T, Kazama A, Koi-zumi H, Takagi M and Tadokoro M. Gliosar-

coma: its origin and morphological pleomor-

phism. St Marianna Med J 2004; 32: 227�234.16� ���� Gliosarcoma. Clinical Neuroscience2002; 20: 624�625.

17� Grant JW, Steart PV, Aguzzi A, Jones DB andGallagher PJ. Gliosarcoma: an immunohisto-

chemical study. Acta Neuropathol �Berl� 1987;79: 305�309.

18� Kochi N and Budka H. Contribution of histio-cytic cells to sarcomatous development of the

gliosarcoma. An immunohistochemical study.

Acta Neuropathol �Berl� 1987; 73: 124�130.19� Schi#er D, Giordana MT, Mauro A and

Migheli A. GFAP, FVIII�RAg, laminin, andfibronectin in gliosarcomas: an immunohisto-

chemical study. Acta Neuropathol �Berl� 1984;63: 108�116.

20� Albrecht S, Connelly JH and Bruner JM. Dis-tribution of p53 protein expression in gliosar-

comas: an immunohistochemical study. Acta

Neuropathol �Berl� 1993; 85: 222�226.21� Frankel RH, Bayona W, Koslow M and New-

comb EW. p53 mutations in human malignant

gliomas: comparison of loss of heterozygosity

with mutation frequency. Cancer Res 1992; 52:

1427�1433.22� Boerman RH, Anderl K, Health J, Borell T,Johnson N, Scheithauer BW and Jenkins RT.

The glial and mesenchymal elements of gliosar-

comas share similar genetic alterations. J Neu-

ropathol Exp Neurol 1996; 55: 973�981.23� Biernat W, Aguzzi A, Sure U, Grant JW, Klei-hues P and Hegi ME. Identical mutation of the

p53 tumor suppressor gene in the gliomatous

and the sarcomatous components of gliosarco-

mas suggest a common origin from glial cells. J

Neuropathol Exp Neurol 1995; 54: 651�656.24� Reis RM, Konu-Lebleblicioglu D, Lopes JM,

Kleihues P and Ohgaki H. Genetic profile of

gliosarcomas. Am J Pathol 2000; 156: 425�432.25� Matsuzaki T, Suzuki T, Fujikura K and

Takata K. Nuclear staining for laser confocal

microscopy. Acta Histochem Cytochem 1997;

30: 309�314.26� Peng HZ, Isaacson PG, Diss TC and Pan LX.Multiple PCR analyses on trace amounts of

DNA extracted from fresh and para$n wax

embedded tissues after random hexamer primer

PCR amplification. J Clin Pathol 1994; 47:

605�608.27� Herpers MJHM, Budka H and McCormick D.

Production of glial fibrillary acidic protein

�GFAP� by neoplastic cells: adaptation to themicroenvironment. Acta Neuropathol �Berl�1984; 64: 333�338.

28� Leong AS-Y. Applied immunohistochemistryfor the surgical pathologist 1993� Edward Ar-nold, London.

29� Mechtersheimer G and Moller P. Expression ofthe common acute lymphoblastic leukemia an-

tigen �CD10� in mesenchymal tumors. Am JPathol 1989; 134: 961�965.

30� Parums DV, Cordell JL, Micklem K, HeryetAR, Gatter KC and Mason DY. JC70: a new

monoclonal antibody that detects vascular en-

dothelium associated antigen on routinely

���� �� 400

44

Page 9: St. Marianna University School of Medicineigakukai.marianna-u.ac.jp/idaishi/www/335/06-33-5Masatomo...rol 1974; 33: 456 471. 7 Barnard RO, Bradford TS and Thomas DGT. Gliomyosarcoma:

processed tissue sections. J Clin Pathol 1990;

43: 752�757.31� Katsetos CD, Legido A, Perentes E and MorkSJ. Class III beta-tubulin isotype: a key cyto-

skeletal protein at the crossroads of develop-

mental neurobiology and tumor neuropathol-

ogy. J Child Neurol 2004; 19: 851�866.

32� ����� ������ �� ������ 2004; 22: 28�37.

33� Leung SY, Chan TL, Chung LP, Chan AS,Fan YW, Hung KN, Kwong WK, Ho JW and

Yuen ST. Microsatellite instability and muta-

tion of DNA mismatch repair genes in gliomas.

Am J Pathol 1998; 153: 1181�1188.

�������� 401

45

Page 10: St. Marianna University School of Medicineigakukai.marianna-u.ac.jp/idaishi/www/335/06-33-5Masatomo...rol 1974; 33: 456 471. 7 Barnard RO, Bradford TS and Thomas DGT. Gliomyosarcoma:

Abstract

Histogenesis of Gliosarcoma�A Molecular Pathological Analysis

Masatomo Doi1, Hirotaka Koizumi1, Hiroyoshi Suzuki2,

and Mamoru Tadokoro1

Gliosarcoma is a rare malignant brain tumor �WHO classification, grade IV� that is defined as aglioblastoma admixed with a sarcomatous component. Thus far, four hypotheses have been postulated to

account for the cellular origin of sarcoma, including vascular, meninx, precursor cell, and metaplasia

theories, whereas recent molecular biological studies have suggested the latter two to be most likely. In this

study, we compared these two hypotheses using molecular pathological approaches to determine which

pathway contributes to the histogenesis of gliosarcomas. Double immunofluorescent staining of glial

fibrillary acidic protein �GFAP�� a glial marker, and laminin, a sarcoma marker, was performed in nine

archival gliosarcoma tissues. Consequent laser confocal microscopy detected no “metaplastic” tumor cells

thought to co-express GFAP and laminin. Microsatellite analyses on four loci �D3S1284� D7S507� D10S226� D17S786� were further carried out in five gliosacomas in which glial and sarcomatous components andnon-tumoral area were separately microdissected. Glial and sarcomatous regions of three tumors exhibited

distinct patterns of microsatellite instability, lending strong support to the “precursor cell theory”.In the

other two tumors, however, only the sarcomatous component showed microsatellite instability of one locus,

which could be consistent with the “metaplasia theory”. These collective results raise the possibility that the

cellular origin of sarcomatous component in gliosarcoma may di#er from case to case.

Key words

brain tumor, gliosarcoma, laser confocal microscopy, microdissection, microsatellite

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

2 Department of Clinical Laboratory, Sendai Medical Center

���� ��� 402

46