Vascular Invasion of Colorectal

8/12/2019 Vascular Invasion of Colorectal

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V a s c u l a r I n v a s i o n o f o l o r e c t a la r c i n o m a R e a d i l y V i s ib l e w i t he r t a i n S t a i n s

Tet suya Inou e M. D. M asaki M or i M. D. Re i sh i Sh im ono M . D.Hiroyuki Kuw ano M. D. Ke izo Sugima chi M. D.From the De partm ent of Surgery II Faculty of Medicine Kyushu Universi ty Fukuoka Japa nW e m a d e u s e o f h e m a t o x y l i n a n d e o s i n ( H E ) s ta i n,Ve rhoef f van -Gi eso n s t a i n fo r e l as ti c t i s sue (EVG) , andfac t o r V I I I - r e l a t ed an t i gen (FVII I-RA) to s t a i n t i s sues ex -c i s e d f r o m 9 4 p a t i e n t s w i t h c o l o r e c t a l c a r c i n o m a . O ft h e s e 9 4 , 4 9 d i e d o f d i se a s e w i t h i n t w o y e a r s ( G r o u p I ) ,a n d 4 5 s u r v i v e d f o r fi v e y e a r s o r l o n g e r ( G r o u p I I ) a f t e rs u r g e ry . I n t h e t i s s u e s f r o m b o t h g r o u p s , t h e u s e o f E V Gs t a in r e v e a l e d a h i g h e r i n c i d e n c e o f v a s c u l a r in v a s i o nt h a n w a s s e e n w i t h H E s t ai n . I n G r o u p I , t h e r a te s w e r e2 8 . 6 p e r c e n t a n d 6 1 . 2 p e r c e n t w i t h H E a n d E V G , r e -s p e c t i v e l y , a n d t h o s e in G r o u p I I w e r e 4 . 4 p e r c e n t a n d31 .1 perc en t , r espec t i ve l y . Conve r se l y , t he FVI II -RA s t a i ns h o w e d a d e c r e a s e i n t h e i n c i d e n c e o f v a s c u l a r i n v as i o ni n b o t h g r o u p s . I n G r o u p I , w h e n v a s c u l a r in v a s i o n w a se x a m i n e d i n E V G - s ta in e d t is s u e s, t h e i n c i d e n c e w a s 8 1 . 3p e r c e n t i n c a s e s o f h e m a t o g e n o u s m e t a s t a s e s a n d 2 3 . 5p e r c e n t i n t h o s e w i t h o u t h e m a t o g e n o u s m e t a s t a s e s ( P 4 T h e r e a r er o u t i n e p a t h o l o g y r e p o r t s s h o w i n g t h e l a c k o f v a s-c u l a r in v a s i o n e v e n i n p a t i e n t s w i th a s y n c h r o n o u sl iv e r m e t a s t a si s . T h e s e r o u t i n e s t u d i e s w e r e d o n eo n l y w i th h e m a t o x y l i n a n d e o s i n ( H E ) s t a in . A l-t h o u g h i t i s w e l l k n o w n t h a t s ta i n s f o r e l a s t ic f i b e r sa r e u s e f u l i n r e v e a l i n g v a s c u l a r i n v a s i o n , 5-7 t h e r ea r e f e w d a ta o n p r e c i s e c o m p a r a t i v e r e s u l t s u s i n gAddress reprint requests to Dr. Sugimachi: Department of Sur-gery II, Faculty of Medicine, Kyushu Universi ty, Maidashi 3-1-1,Higashi-ku, Fuku oka 812 , Japan.

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s e r ia l s e c t io n s s t a i n e d b y H E a n d V e r h o e f f v a n -G i e s o n s t a in f o r e l a s t ic t i s s u e ( E V G ) . I n a d d i t io n ,t h e r e a re f e w r e p o rt s c o n c e r n i n g i m m u n o h i s t o -c h e m i c a l s t u d i e s o f v a s c u la r i n v a s i o n o f c o lo r e c t a lc a r c i n o m a u s i n g f a c to r V I I I - r e l a t e d a n t i g e n ( F V I I I -R A ) c o m p o u n d s t ha t s h o w t h e e n d o t h e l i u m o f t h ev a s c u l a r v e s s e l s . 8T h e r e f o r e , w e d i d a r e t r o s p e c t i v e r e v i e w o f d a tao n 9 4 p a t i e n t s w i t h c o l o r e c t a l c a r c i n o m a , t h e o b -j e c ti v e b e i n g t o c o m p a r e t h e i n c i d e n c e s o f v a s c u l a ri n v a s i o n i n t h r e e s e r i a l s e c t i o n s s t a i n e d b y H E ,E V G , a n d F V I I I - R A .

PATIENTS AND METHODSF i n d i n g s i n 9 4 p a t i e n t s w e r e e x a m i n e d r e t r o -

s p e c t iv e l y . A ll h a d u n d e r g o n e s u r g ic a l r e s e c t i o nf o r c o l o r e c t a l c a r c i n o m a i n t h e D e p a r t m e n t o f S u r-g e r y I I, K y u s h u U n i v e r s i ty H o s p i t a l, b e t w e e n 1 9 78a n d 1 9 8 3. O f t h e s e 9 4 p a t i e n t s , 4 9 d i e d o f d i s e a s e( r e c u r r e n c e a n d / o r m e t a s t a s i s ) w i t h in t w o y e a r sa f t e r t h e s u r g e r y ( G r o u p I ) . F o r ty - f iv e p a t i e n t s s u r -v i v e d m o r e t h a n f iv e y e a r s a ft e r s u r g e r y w i t h o u te v i d e n c e o f d i s e a s e ( G r o u p I I ) . G r o u p I w a s d i-v i d e d i n t o t w o g r o u p s : G r o u p I A (3 2 p a t ie n t s )d e v e l o p e d h e m a t o g e n o u s d i st a nt m e t a s ta s e s to th el iv e r , l u n g , b r a i n , a n d b o n e , a s n o t e d a t t h e t i m e o fd e a t h , a n d G r o u p I B ( 1 7 p a t i e n t s ) h a d n o d i s t in c te v i d e n c e o f h e m a t o g e n o u s d i st a nt m e t a s ta s e s . T h el a tt e r d i e d o f lo c a l r e c u r r e n c e s , l y m p h n o d e m e t a s -t a se s , a n d / o r p e r i t o n e a l d i s s e m i n a t i o n . A ll d is t a n tm e t a s t a s e s o r r e c u r r e n c e s w e r e i n v e s t i g a t e d u s i n gc o m p u t e d t o m o g r a p h y , e c h o g r a p h y , b o n e s c i n t i g -r a p h y , a n d c h e s t x - r a y . F o r a ll t h e s e p a t i e n t s , a d e -q u a t e p a t h o l o g i c m a t e r i a l s a n d f o ll o w - u p d a t a w e r ea v a i l a b l e .

A ll s u r g ic a l s p e c i m e n s h a d b e e n f i x e d in 1 0p e r c e n t n e u t r a l f o r m a l in a n d r o u t in e l y p r o c e s s e df o r p a r a f fi n e m b e d d i n g . I n t hi s s tu d y , o n e t o th r e eb l o c k s fo r e a ch p r i m a r y t u m o r w e r e u s e d. T h r e e


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36 INOUE ET LTable 2.

Incidence of Vascular Invasion

Dis Colon Rectum, January 1992

StainingsH E EVG FVIII-RA

Group I(n = 49) 28.6 (14/49) 61.2 (30/49) 8.0 (4/49)Group IA (n = 32) 31.3 (10/32) 81.3 (26/32)* 9.4 (3/32)Group IB (n = 17) 23.5 (4/17) 23,5 (4/17)* 5.9 (1/17)Group II (n = 45) 4.4 (2/45) 31.1 (14/45) 2.0 (1/45)

Group I: patients died of disease within two years after surgery. Group IA: patients died mainly of hematogenousmetastasis. Group IB: patients died mainly of loca l recurrences, lymph node metastases, or peritoneal dissemination.Group I1: patients survived five years or more after surgery.* The correlation between Groups IA and IB showed a statistical difference (P < 0.01).

T h e i n c i d e n c e o f v a sc u l a r in v a s i o n i n G r o u p s Ian d I I i s g iv en in Tab le 2 . I n b o th g r o u p s , t h ei n c i d e n c e o f v a s c ul a r i n v a s i o n w i t h t h e u s e o f EV Gsta in was h ig h e r t h an th a t see n wi th H E s t a in. I nco n t r a s t , t h e in c id e n ce o f v a scu la r i n v as io n wi thth e u se o f FVI I I - R A s t a in was r em ar k ab ly lo werth an th a t seen wi th H E s t a in . I n t h e Gr o u p Ip a t i e n t s w i t h a p o o r p r o g n o s is , t h e i n c i d e n c e o fv ascu la r i n v as io n wi th EVG s t a in was ab o u t tw iceth a t see n wi th H E s ta in . In t h e Gr o u p I A p a t i en t s ,i n w h o m a h e m a t o g e n o u s m e t a s t a s i s o c c u r r e d , t h ei n c i d e n c e o f v a s c u la r i n v a s i o n w as t h e h i g h e s t,w h i l e , i n G r o u p I B p a t i e nt s , w h o s h o w e d n o e v i-d e n c e o f a n y di s t an t m e t a s t a s es , t h e i n c i d e n c e d e -t ec t ed b y EVG s t a in was th e sam e a s t h a t seen wi thH E s ta i n. W h e n t h e E V G s e c t i o n s w e r e u s e d f o rt h e i d e n t i fi c a t i o n o f v a s c u la r i n v a s i o n, t h e r e w e r es i g n i fi c a n t d i f fe r e n c e s b e t w e e n G r o u p s I A a n d I B( P < 0 . 0 1) ; h o w e v e r , w h e n r o u t i n e H E s e c t i o n so n l y w e r e u s e d , t h e r e w e r e n o s i g n i f i c a n t di ff e r-e n c e s .

I n th e H E sec t io n s , d e t e c t io n o f v a scu la r i nv a -s i o n w a s m o s t d i f f i c u l t i n a r e a s w h e r e t h e t u m o rc e l l s g r e w c o m p a c t l y a n d d e n s e l y w i t h l it t le s t r o m a( F ig . 1 ). M a n y o f t h e c o l o r e c t a l c a r c i n o m a s w e r ew e l l - o r m o d e r a t e l y - d i f f e r e n t i a t e d a d e n o c a r c i n o -m a s , s h o w i n g c o m p a c t a n d d e n s e l y g r o w i n g c a n c e rce l ls . In contrast , in the EVG sec t ions, a b lack-s t a in ed r im o f e l a s t i c f i b e r s was c l ea r ly v i s ib l e ,m a k i n g t h e d e t e c t i o n o f v a s c ul a r i n v a s i o n e a s i e r i na r ea s wi th a co m p ac t g r o w th o f ce l l s ( F ig . 1 ) . I nG r o u p I B, t he i n c i d e n c e o f v a s c u la r i n v a s i o n w ase q u a l b e t w e e n H E a n d E VG . T h e f r e q u e n c y o fp o o r l y d i f f e r e n t i a t e d a d e n o c a r c i n o m a w a s r e l a -t i v e l y h i g h i n G r o u p I B. D e t e c t i o n o f v a s c u l a rin v as io n in H E sec t io n s was n o t a s d i f f i cu l t i nc a se s o f p o o r l y d i f f e r en t i a t e d a d e n o c a r c i n o m a w i t h

Figure 1. Left detection of vascular invasion is difficultusing H E stain (x9 0). Right: detection of vascular inva-sion is easy in the same area in the tissue sample (EVG,x90). Arrows indicate vascular invasion.

l o o s e c a n c e r o u s t i s s u e a n d a w i d e s t r o m a . T h es t a in in g o f FVI II - RA was s p ec i f i c t o t h e en d o t h e -l iu m o f cap i l l a r i e s , v e in s , an d a r t e r i e s . I n v e sse l sw i t h t u m o r i n v o l v e m e n t , t h e s t a i n in g o f F V I II -R Awas e i th e r l o s t o r weak ( F ig. 2 ) . P r e su m a b ly , t h i si s d u e t o d e s t r u c t i o n o f t h e v as c u l a r e n d o t h e l i u mb y t u m o r c e l l s o c c u p y i n g t h e l u m e n ( F ig . 3 ).T h e r e f o r e , t h e i n c i d e n c e d e t e c t e d b y F V I II -R A w a sl o w i n e a c h g r o u p .

I n Tab le 3 , v a scu la r i n v as io n d e t ec t ed in t h e EVGs e c t i o n s w a s e v i d e n t a c c o r d i n g t o t h e s i te o f t h eex te n t o f v a scu la r i n v as io n in to th e co lo r ec t a l wa l l.T h i r t e e n o f 1 4 p a t i e n t s i n G r o u p I I h a d i n t r a m u r a lv ascu la r i n v as io n , wh i l e , i n Gr o u p I , 8 0 p e r cen t o ft h e v a s c u l a r i n v a s i o n w a s e x t r a m u r a l . T h e r e w e r es i g n i fi c a n t d i f f e r e n c e s b e t w e e n G r o u p s I a n d I Iw i t h r e g a r d t o t h e s e f i n d i n g s ( / ' < 0 . 0 1) . T h e r ew e r e n o s i g n i f i c a n t d i f f e r e n c e s b e t w e e n G r o u p s I Aand IB.


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Vol. 35, No. 1 VASCULAR INVASION IN COLORECTAL CANCER 37D I S C U S S I O N

W h e n v a s c u l a r i n v a s io n b y m a l i g n a n t c e l l s i sp r e s e n t , l i v er m e t a s t a se s w i l l o c c u r t h r e e t i m e sm o r e f r e q u e n t l y t ha n i n th e a b s e n c e o f t h e s ec e l ls , l 'z H o w e v e r , t h e r e p o r t e d i n c i d e n c e o f va s-cu la r in vasio n var ies con sid era b ly . >6'1~ 11 On e rea-so n f o r t h e v a r i ab i l i t y i s t h e d i f f e r e n ce in t h e n u m -

Figure 2. Note the weakly positive staining for FVIII-RA inthe lumen of the vascular vessel involved with tumor cellsABC method, x170).

Figure 3. Vascu lar invasion is detected with EVG left,xg0) but is not visible with FVlII-RA right, x90).

b e r o f e x a m i n e d s e c t i o n s ; w i t h t h e i r i n c r e a s e , t h ef r e q u e n c y o f v a s cu la r i n v as io n in c r ea se s . 2' 12 W h i l ed i f f e r e n c e s i n t e c h n i q u e s u s e d a l s o n e e d t o b eco n s id e r ed , 2'13 in s o m e in s t i t u t io n s , sp ec i a l s t ain -in g f o r e l a s t i c f ib e r s su ch a s EVG is r o u t in e ly u sedt o d e t e r m i n e t h e p a t h o l o g y , e s p e c i a l l y f o r t h e d e -t ec t io n o f v a scu la r i n v as io n . 14 Th e f r e q u e n c y o fv a s c u la r i n va s i o n m a y in c r e a s e w i t h t h e c o m b i n e du se o f sp ec i a l s t a in s.

Th e u se f u ln ess o f t h e e l a s t i c t i s su e s t a in is co n -t rovers ia l . Min sky and Mies 15 s ta te d tha t the e las t ict i s s u e s t a i n w a s i m p o r t a n t b e c a u s e t h e r e w e r e d e -c r ea se s i n t h e f a l se - n eg a t iv e r a t e s an d b ecau se v as -c u l a r i n v a s i o n c o u l d b e d i f f e r e n t i a t e d f r o m l y m -p h a t i c v e s s e l i n v a si o n . 6 O n t h e o t h e r h a n d , B u r n sand Pfaf f16 s t a t ed th a t r o u t in e H E sec t io n s w e r ea d e q u a t e i n m o s t i n s ta n c e s , a l t h o u g h t h e y u s e de l a s t i c t i s s u e s t a i n w h e n n e c e s s a r y . T a l b o t e t a l 1~c o n s i d e r e d t h e e l a s ti c t i s su e s t a i n t o b e r a r e l y h e l p -f u l . Th e r ec t a l wa l l co n ta in s a l a r g e am o u n t o fb a c k g r o u n d f i b e r w i t h s t a i n in g c h a r a c te r i s ti c s o fe l a s t i c t i s su e ; t h us , t h e u se f u ln ess o f t h e se s t a in swas l im i t ed . I n o u r s tu d y , t h e r ec t a l wa l l d id co n -t a in a l a r ge a m o u n t o f b l a c k - s t a i n e d f i b e r i n s o m ecases , b u t i t was n o t d i f f i cu l t t o d i f f e r en t i a t e a b l ack -s t a in ed r im o f v a scu la r i n v as io n f r o m a l a rg ea m o u n t o f b a c k g r o u n d f i b e r i f a t t e n t i o n w a s d i -r e c t e d t o t h e f o r m o r d i r e c t i o n o f t h e b l a c k - s t a in e df ibers .I n th e cu r r en t s tu d y , t h e ad d i t i o n a l u s e o f e l a s ti ct i s s u e s t a i n f o r r e p r e s e n t a t i v e s e c t i o n s p r o v e d t ob e p r ac t i ca l an d u se f u l . T h e u s e o f EVG s t a in in -c r ea s ed th e in c id en c e o f v a scu la r i n v as io n , p ar t i c -u l a r l y i n p at i e n t s w i t h a d i s t a nt h e m a t o g e n o u s m e -t as ta s is ( G r o u p I A ), w h e r e t h e i n c i d e n c e i n c r e a s e df r o m 3 1 .3 p e r c e n t b y H E t o 81 .3 p e r c e n t b y EV G .Us in g o n ly H E s t ain f o r i d en t i f i c a t io n o f v a scu la ri n v a si o n , t h e c o r r e l a t i o n b e t w e e n d i s t a nt h e m a t o g -e n o u s m e t a s t a s i s a n d v a s c u l a r i n v a s i o n w a s n o t

Table 3.Site of the Extent of Vascular Invasion into the Colorectal Wall

IntramuralMucosa Submucosa

Extramural IncidenceMuscle Subserosa or of VascularLayer Adventitia Invasion

Group I n = 49) 0 2 4 24 30/49Group IA n = 32) 0 2 4 20 20/32Group IB n = 17) 0 0 0 4 4/17Group II n = 45) 3 9 1 1 14/45

There were significant differences between Grou ps I and II P < 0.01) and between Grou ps IA and II P < 0.01).* Vascular invasion was detected in EVG sections.


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Vascular Invasion of Colorectal