D . Manoj Kuma Yada e al. Role o CD44 And MMP2 Ma ke in Diagnosis and P ognosis o U ina y Bladde
Ca cinoma. In . J Med. Pha m. Res., 6 (6): 193-200, 2025
193
In e na ional Jou nal o Medical
and Pha maceu ical Resea ch
Online ISSN-2958-3683 | P in ISSN-2958-3675
F equency: Bi-Mon hly
A ailable online on: h ps://ijmp .in/
O iginal A icle
Role o CD44 And MMP2 Ma ke in Diagnosis and P ognosis o U ina y
Bladde Ca cinoma
D . Manoj Kuma Yada 1, D . CH Pawan P a ap Singh2, D Ha i P asad3
1 MD, Assis an P o esso Depa men o Pa hology, Au onomous S a e Medical College, Sonebhad a UP, India.
2 MD, Assis an P o esso Depa men o Pa hology, D . KNS Memo ial Ins i u e o Medical Sciences, Ba abanki, UP, India.
3 PhD, Assis an P o esso Depa men o Ana omy, Au onomous S a e Medical College, Sonebhad a UP, India.
A B S T R A C T
Co esponding Au ho :
D . CH Pawan P a ap Singh
MD, Assis an P o esso
Depa men o Pa hology, D .
KNS Memo ial Ins i u e o
Medical Sciences, Ba abanki,
UP, India.
Recei ed: 12-10-2025
Accep ed: 28-10-2025
A ailable online: 10-11-2025
In oduc ion: Lowe u ina y ac symp oms a e caused by se e al ac o s. I a pa ien
su e ing om equen u ina ion associa ed wi h pain and blood in u ine d aws he
a en ion o pa ien s and b ings hem o consul a ions wi h he clinicians. Among
se ious causes o lowe u ina y ac symp oms is bladde ca cinoma, a ec ing mo e
men (3.67%) and compa a i ely ewe (0.83%) women. Clinicians, wi h he help o
pa hologis s, con i m hei diagnosis o decide on he choice o ea men op ions o
be e quali y o li e o he pa ien s. Pa hologis s accomplish his opa hology and
subsequen use o CD44 and MMP2 an ibodies as diagnos ic and p ognos ic ma ke s
in u ina y bladde ca cinoma. Enables u ologis s o choose be e ea men op ions o
imp o e he quali y o li e o he su e e .
Aim: This s udy was aimed a de e mining he sensi i i y and speci ici y o CD44 and
MMP2 o he diagnosis and p ognosis o u ina y bladde ca cinoma.
S udy Design: P ospec i e c oss sec ional analy ical s udy design was chosen.
Ma e ial and Me hods: O e all, 56 his opa hological specimens we e aken o s udy
om men and women be ween he ages o 18 and 60 yea s. The issue was ecei ed
a e ansu e h al esec ion o bladde issue (TURBT) and adical cys ec omy om
he u ology depa men . The issues a e ixa ion in 10% bu e ed o malin solu ion,
g ossing and sec ioning we e made. Thin sec ions o 4- o-6-mic on hickness we e
p epa ed. Following s anda d issue p ocessing p o ocol, haema oxylin and eosin
s aining was done. The Dako immunohis ochemis y p o ocol was ollowed o he
posi i i y o he p epa ed and s ained sec ions o liquid an i-CD44 an ibody
[ERP1013Y] ab51037 and an i-MMP2 an ibody ab3750 eagen s in 1:70 dilu ion.
Then each sec ion was examined unde a mic oscope in high powe a 100X.
Resul s and Obse a ions: SPSS e sion 21 so wa e was used o da a analysis.
Mean age ± SD o pa ien s was 55.07±11.99 yea s. Bladde ca cinoma was ound
highes (46.4%) in pa ien s o age g oup 60 yea s o mo e. Among s udy g oups, males
cons i u ed 50 (89.3%) and emales 6 (10.7%). The CD44 exp ession was signi ican ly
less in high g ade han in low g ade (p<0.001). The highly signi ican associa ion was
ound be ween MMP2 exp ession and umou g ades (p=0.006). The MMP2
exp ession was signi ican ly mo e in he high g ade han he low g ade (p=0.001). In
he p esen s udy, sensi i i y was 89.2% (% accu acy o p edic ion o high g ade.
Speci ici y obse ed was 100% (% accu acy o p edic ion o low g ades). O e all
diagnos ic accu acy epo ed 92.9% (% accu acy o ue p edic ion).
Conclusion: CD44 exp ession is signi ican ly mo e exp essed in low g ade non-
in asi e u o helial ca cinoma (NMIBC) while MMP2 is signi ican ly mo e exp essed
in high g ade muscle in asi e u o helial ca cinoma (MIBC). The e o e, bo h CD44
and MMP2 is eliable and an excellen diagnos ic bioma ke ma ke .
Copy igh © In e na ional Jou nal o
Medical and Pha maceu ical
Resea ch
Keywo ds: MMP2 (ma ix me allop o einase), An i-CD44 an ibody [ERP1013Y]
AB51037, An i-MMP2 an ibody AB37150 and Ro a y Mic o ome, Radical cys ec omy,
T ans U e h al esec ion o bladde Tissue (TURBT).
D . Manoj Kuma Yada e al. Role o CD44 And MMP2 Ma ke in Diagnosis and P ognosis o U ina y Bladde
Ca cinoma. In . J Med. Pha m. Res., 6 (6): 193-200, 2025
194
INTRODUCTION
U ina y bladde is common si e o cance de elopmen in u ina y ac . In India acco ding o ecen epo s o Na ional
Cance Regis y P og amme 2006, he o e all inciden a e o u ina y bladde cance is 2.25% (pe 100000 annually) [1].
Gende wise p e alence is 3.67% among males and 0.83% o emales [1]. Among all malignancies, u ina y bladde
ca cinoma anks ele en h, and i s incidence is ising, acco ding o GLOBOCAN 2020 wo ld ac shee da a. I has also been
shown ha he Indian popula ion is on he ise. By 2040, he e will be 79.6% mo e cases o u ina y bladde cance (UBC)
in India, acco ding o GLOBOCAN 2020[2]. In Wes e n Eu opean na ions and he Uni ed S a es, he li e ime isk o whi e
males and emales anges om 1 in 80 and 1 in 25, espec i ely. E e y yea , abou 145,000 indi iduals globally die ou
due o bladde cance [3].
The u o helium o ansi ional epi helium is he loca ion whe e he majo i y o bladde cance s s a . Based on
epidemiological in es iga ions, cance p ima ily a ec s olde men, and he p esence o mucosal i i an s could inc ease he
exc e ion o ca cinogenic chemicals and pa asi e in ec ions in he u ine. A numbe causa i e ac o s o ac o s a e included
ha can be esponsible o u ina y bladde ca cinoma. As mos o he people in no h India occupa ionally belonged o
ag icul u e. Among hese mos o he people a e smoke [4] and secondly, hey a e exposed o chemicals like an h anilic
diamide, chlo py iphos cype me h in, lesen a, and icyclazole we e he pes icides/ insec icides commonly used in
ag icul u e [5]. The e is also e idence ha pa asi ic in ec ion specially schis osomiasis cause u ina y bladde malignancy
[6].
CD44 a complex ans-memb ane glycop o ein, also called by mul iple names like He mes an igen, homing cell adhesion
molecule, HUTCH-1, phagocy ic glycop o ein-1, lymphocy es -homing ecep o , and ECM III, is coded by he CD44 gene
on ch omosome 11[7], which consis s o 20 exons [8]. T ansc ip s o CD44 gene unde go complex al e na i e splicing,
which esul s in many unc ionally dis inc iso o ms, such as CD44 s anda d iso o m (CD44s) and CD44 a ian iso o m
(CD44 ) [9]. CD44s a e ound in mos o he human body cells [10], while CD44 is exp essed p ima ily on cells du ing
in lamma ion and on umo cells. CD44 p o ein consis o a sho C- e minal cy oplasmic domain, a ans- memb ane
domain, and se en ex acellula domain which con ain an N- e minal Hyalu onic acid binding link-homology module and
s em egion [11,112].
CD44 plays pi o al ole in p omo ing umo in asion and me as asis by con ibu ing o adhesion o umo cells o
endo helium and ib onec in en iched ma ices [13]. CD44 possessed selec in ligand ac i i y. Exp ession o CD44 bo h
in b eas cance and colon cance cells enhanced adhesion o endo helial cells and ib onec in co ela e i s me as a ic
po en ial [14,15]. CD44 po en ia ed he adhesion o basal –b eas cance cell o endo helium and ib onec in in an alpha
5B1-in eg in dependen manne , while CD44 knockdown a enua ed adhesion abili y [13].
Ma ix me allop o einases (MMPs) a e a la ge amily o Zinc dependen p o eoly ic enzyme, manly in ol ed in he
deg ada ion o p o ein a ge s, ha a e componen o he ex acellula ma ix. MMPs play a di e se and c ucial ole in
no mal physiological p ocess such as issue emodeling, emb yonic de elopmen and ep oduc ion. The MMPs amily
consis s o a leas 26 o 28 membe s and mos MMPs a e composed o se e al dis inc domains, a ca aly ic domain (MMP7
and MMP26), N e minal p odomains (also e med p opep ide) and a hemopexin-like C e minal domain connec ed by
linke o hinge egion, and o he s ha e addi ionally had ib onec in-like domain (MMP2 and MMP9) ha a e c ucial o
hei ac i i y, and subs a e speci ici y. MMPs can deg ade he ex acellula ma ix (ECM), and can con ol he o ma ion
o umo blood essels [10].
Image-2.1A: H/E Low G ade a 40X. Image-2.1B: H/E low G ade a 100X
The p esen s udy was aimed a o de e mine he ole o CD44 and MMP2 as a diagnos ic and p ognos ic ma ke s in u ina y
bladde ca cinoma. The s udy was also p ima ily ocused on p ima y ou come o i s sensi i i y and speci ici y in he
exp ession pa e n o CD44 and MMP2 in muscle in asi e ca cinoma wi h non-muscle in asi e u ina y bladde ca cinoma.
D . Manoj Kuma Yada e al. Role o CD44 And MMP2 Ma ke in Diagnosis and P ognosis o U ina y Bladde
Ca cinoma. In . J Med. Pha m. Res., 6 (6): 193-200, 2025
195
MATERIAL AND METHODS
Be o e conduc ing s udy ins i u ional e hical clea ance (IEC) was aken om King Geo ge’s Medical Uni e si y Lucknow,
U a P adesh. A c oss sec ional analy ical p ospec i e s udy design was chosen in hospi al se ing. The s udy was
conduc ed in collabo a ion wi h Depa men o Pa hology and he Depa men o U ology o he King Geo ge’s Medical
Uni e si y be ween 2018 o 2019 o e a pe iod o one yea .
A o al o 56 male and emale pa ien s we e included in he s udy a e aking w i en in o med consen . Among 56 pa en s
50 we e males and 6 we e emales. The age o pa icipan s was 18 yea s o mo e han 60 yea s. These s udy g oup
pa icipan s we e selec ed based on clinical his o y o suspicion o u ina y bladde ca cinoma diagnosed by cys oscopy,
pe -abdominal ul asonog aphy (USG) and con as enhanced compu ed omog aphy abdomen (CECT).
Inclusion c i e ia we e biopsy o he issue ob ained om pa ien who we e ope a ed upon ansu e h al esec ion o bladde
issue (TURBT) and adical cys ec omy wi h clinical suspicion o u ina y bladde ca cinoma. The su gical p ocedu e was
pe o med by U ologis in U ology Depa men . Exclusion c i e ia we e inadequa e sample issue and pa ien s who we e
no gi en w i en in o med consen .
As soon as bladde issue esec ed ollowed by su gical p ocedu e TURBT o adical cys ec omy, specimens we e kep in
10% bu e ed o malin solu ion o 24 hou s o ixa ion. Smalle co e biopsies we e g ossed on same day o ecei ing.
While bigge biopsies specimens we e allowed o ix o e nigh in 10% neu al bu e ed o malin. Thin sec ion o 4- o-6-
mic on hickness we e p epa ed using manual o a y mic o ome. These we e s ained ou inely wi h hema oxylin and eosin.
Using Ca ousal ype o issue p ocesso s anda d s eps o issue p ocessing (i) ixa ion, (ii) dehyd a ion, (iii)clea ing, (i )
in il a ion and ( i) embedding we e adop ed. His opa hological examina ion was done. G ading he lesion was in o muscle
in asi e ca cinoma (MIBC) and non-in asi e bladde ca cinoma (NMIBC) based on AJCC 8 h edi ion [16] guidelines was
made.
Pa hologic S age classi ica ion (pTNM, AJCC 8 h Edi ion) [16]
pTX
P ima y umou canno be assessed
pT0
No e idence o p ima y umou
pTa
No in asi e papilla y ca cinoma
pTis
U o helial ca cinoma in si u:( la umou )
pT1
Tumou in ade lamina p op ia (subepi helial connec i e issue)
pT2
Tumou in ades muscula is p op ia
pT2a
Tumou in ades supe icial muscula is p op ia (inne hal )
pT2b
Tumou in ades deep muscula is p op ia (ou e hal )
pT3:
Tumou in ades pe i- esical so issue
pT3a
Tumou in ades pe i- esical so issue mic oscopically
pT3b
Tumou in ades pe i- esical so issue mac oscopically (ex a esical mass)
pT4
Ex a esical umou di ec ly in ades any o he ollowing: p os a ic s oma, seminal esicles, u e us, agina,
pel ic wall, abdominal wall
pT4a
Ex a esical umou di ec ly in ades any o he ollowing: p os a ic s oma, seminal esicles, u e us o
agina.
pT4b
Ex a esical umou di ec ly in ades pel ic wall, abdominal wall
Regional lymph nodes (pN) [16]
pNX
Lymph nodes canno be assessed
pN0
No lymph node me as asis
pN1
Single egional lymph node me as asis in he ue pel is (pe i esical, ob u a o , in e nal and ex e nal iliac
o sac al lymph node)
pN2
Mul iple egional lymph node me as asis in he ue pel is (pe i esical, ob u a o , in e nal and ex e nal
iliac o sac al lymph node me as asis)
pN3
Lymph node me as asis o he common iliac lymph nodes.
Dis an Me as asis (pM)[16]
pM1
pM1: Dis an me as asis
pM1a
Dis an me as asis limi ed o lymph nodes beyond he Common iliacs.
PM1b
Non-lymph node dis an me as ases
Dako Immunohis ochemis y P o ocol was ollowed
D . Manoj Kuma Yada e al. Role o CD44 And MMP2 Ma ke in Diagnosis and P ognosis o U ina y Bladde
Ca cinoma. In . J Med. Pha m. Res., 6 (6): 193-200, 2025
196
I. DEPARAFFINIZATION: was done by keeping in xylene o p e iously 3-5-mic on hick cu sec ion which we e ixed
a 560 C o 20 minu es. These sec ions we e ehyd a ed h ough g aded alcohols ollowed by dis illed wa e o 5
minu es in each.
II. UNMASKING OF ANTIGENIC SITES BY PRESSURE COOKER ANTIGEN RETRIEVAL METHOD:
depa a inized sec ions we e placed in TRIS-EDTA (TRIS-1.121gm, EDTA0.37gm and ween 20-500µl) bu e o
an igen e ie al a 980 C o 25 minu es and hen cooled a oom empe a u e. I was ollowed by 3 gen le washes in
is o 5 minu es each.
III. PEROXIDASE TREATMENT: Sec ions we e ea ed wi h 3% hyd ogen pe oxide o 10 minu es o block endogenous
pe oxidase ac i i y. I was ollowed by 3 gen le washes in TRIS bu e ed saline (ph. 7.4) o 5 minu es each.
IV. PRIMARY ANTIBODY: Slides we e wiped o and incuba ed o 90 minu es wi h p ima y an ibody a 40 C in a mois
chambe . Slides we e insed wi h TRIS EDTA bu e (ph. 9) h ice.
V. BIOTINYLATED LINK ANTIBODY (DacoEnVisionFlexTM): Excess bu e was wiped o and sec ions we e co e ed
wi h link an ibody(seconda y) o 30 minu es a oom empe a u e.
VI. ENZYME CONJUGATE: Enzyme conjuga e (s ep a idin ho se Redish pe oxidase) was applied o 30 minu es
ollowed by 3 washes in TBS o 5 minu es each.
VII. SUBSTRATE CHROMOGEN SOLUTION: Concen a ed Diaminobenzene (DAB) solu ion was dilu ed wi h
subs a e bu e (500µl subs a e bu e + 2 d ops DAB)
VIII. COUNTERSTAINING: Sec ions we e dipped in 10% haema oxylin 2-5 imes and washed in dis illed wa e o 5
minu es ollowed by moun ing o sec ion in DPX. P esence o b own colou ed end p oduc a he si e o a ge an igen
was indica i e o posi i e eac i i y.
U ilized an ibody in he p esen s udy was 1. An i- MMP2 an ibody ab37150 in liquid o m. Dilu ion used was 1:70 and
incuba ed o e a pe iod o 90 minu es. I s ains a cy oplasm le el on posi i e eac i i y. This an ibody is species speci ic
o a , mouse, chicken and Human. 2. An i-CD44 an ibody [ERP1013Y] ab51037 was also used in liquid o m. Dilu ion
used was 1:70 and incuba ed o 90 minu es.CD44 an ibody s ains a plasma memb ane le el on posi i e eac i i y. CD44
an ibody was conside ed posi i e con ol o human b eas ca cinoma issue and human u ina y bladde . While MMP2
an ibody was conside ed posi i e con ol o human neu o ib oma.
Image-2.1C: H/E High G ade a 40X. Image-2.1D: H/E High G ade a 100X
RESULTS AND OBSERVATIONS
The s a is ical analysis was done by using SPSS e sion 21. Mean and s anda d de ia ion we e calcula ed. Chi squa e es
and s uden ‘ ’ es was employed. Sensi i i y, speci ici y, posi i e p edic i e alue (PPV), nega i e p edic i e alue (NPV)
and accu acy was calcula ed. To minimize bias s udy g oups we e s a i ied in 118-29yea , 30-39 yea s, 40-49 yea s, 50-
59yea s and mo e han 60 yea s, The o e all mean age was 55.07±SD11.99 yea s (18-75) including male and emale
pa ien s. Mos o he case belonged o age 60 yea s o mo e which cons i u ed 46.4% (26 ou o 56). Only 3.6% (2 ou o
56) cases we e aged below 30 (age g oup 18-29) yea s.
Table no -1.1 Dis ibu ion o p ocedu es along wi h cases among s udy subjec s
P ocedu es
Cases
F equency (%)
P ocedu e Done
Cys oscopy
19 (33.9%)
Pe -abdominal USG
24 (42.9%)
CECT
13 (23.2%)
Tissue
Radical Cys ec omy
3 (5.4%)
TURBT
53 (94.6%)
His ology
High g ade Lamina In asi e
11 (19.6%)
High g ade Muscle In asi e
22 (39.3%)
Low g ade Lamina In asi e
11 (19.6%)
Low g ade Supe icial
12 (21.4%)
D . Manoj Kuma Yada e al. Role o CD44 And MMP2 Ma ke in Diagnosis and P ognosis o U ina y Bladde
Ca cinoma. In . J Med. Pha m. Res., 6 (6): 193-200, 2025
197
G ade
Low G ade
23 (41.1%)
High G ade
33 (58.9%)
Dis ibu ion o cases acco ding o issue emo al p ocedu e he adical cys ec omy was 5.4% (3/56) and he TURBT 94%
(53/56). The maximum cases we e o he high-g ade muscle in asi e 39.4% (22/56) ollowed by 21.4% (12/56) low g ade
supe icial. While Low g ade lamina in asi e and high-g ade lamina in asi e u o helial ca cinoma we e in equal
p opo ion 19.6% (11/56) each espec i ely. Low g ade ca cinoma was ound in 41.1% (23/56) cases. High g ade ca cinoma
was ound in 58.9% (33/56).
Table 1.1a Showing Dis ibu ion o cases acco ding o CD44 exp ession
CD44
Exp ession
To al
Low G ade
High g ade
Signi icance
No.
No.
%
No.
%
Chi Sq
p- alue
Sco e 1
15
0
0%
15
100%
42.47
<0.001
Sco e 2
22
4
18.2%
18
81%
Sco e 3
19
19
100%
0
0%
Table 1.1a shows Sco e 1 o CD44 exp ession was seen in 15 cases wi h all he high g ades. Sco e 2 was seen in 22 cases
wi h 18.2% low and 81.8% high g ades. While sco e 3 was seen in 19 cases wi h all low g ades. The highly signi ican
associa ion was ound be ween CD44 exp ession and umou g ades (p< 0.001). When compa ison o exp ession be ween
high and low g ades ca cinoma was made hen he mean CD44 exp ession alue among low g ade umou was
2.83±SD0.388 while o high g ade ca cinoma i was 1.55±SD0. 506.The CD44 exp ession was signi ican ly less in high
g ade han he low g ade (p<0.001).
Table 1.1b Showing Dis ibu ion o cases acco ding o MMP2exp ession
MMP2
Exp ession
To al
Low G ade
High g ade
Signi icance
No.
No.
%
No.
%
Chi Sq
p- alue
Sco e 1
12
9
75.0%
3
25.0%
10.39
0.006
Sco e 2
33
13
39.4%
20
60.6%
Sco e 3
11
1
9.1%
10
90.9%
Table 1.1b shows Sco e 1 o MMP2 was seen in 12 cases wi h 25% high g ades and 75% low g ades. Sco e 2 was seen in
33 cases wi h 39.4% low and 60.6% high g ades. While Sco e 3 was seen in 11 cases wi h 9.1% low g ades and 90.9%
high g ades. The highly signi ican associa ion was ound be ween MMP2 exp ession and umou g ades (p=0.006). when
compa ison o MMP2 exp ession be ween high g ade and low g ades ca cinoma was made he mean exp ession alue
among low g ade was 1.65±SD0.57while o high g ade ca cinoma i was 2.21±SD0.60. The MMP2 exp ession was
signi ican ly mo e in high g ade han he low g ade (p=0.001).
To show co ela ion be ween CD44 and MMP2 exp ession spea man co ela ion coe icien (ρ) es was done. This showed
signi ican nega i e co ela ion (ρ=-0.426, p=0.001) be ween CD44 and MMP2exp ession. I means when he alue o
CD44 inc eases, he alue o MMP2 dec eases. When logis ic eg ession analysis o p edic umou g ade on he basis o
CD44 and MMP2 exp ession i gene a ed equa ion PG = −22 ⋅13(CD44)+ 1.56(MMP2)+43.01. High g ade will be
p edic ed when PG>0, else low g ade will be p edic ed. A signi ican high ag eemen (k=0.848, <0.001) was ound be ween
p edic ed g ade and ac ual g ade as ound in his opa hology.
Table 1.1c Showing alidi y summa y o logis ic eg ession analysis
Sensi i i y
89.2%
Speci ici y
100%
Posi i e P edic i e alue (PPV)
100%
Nega i e P edic i e alue (PPV)
82.6%
Diagnos ic Accu acy
92.9%
Clea om able 1.1c ha his p edi e model has sensi i i y 89.2 (% accu acy o he p edic ion o high g ade), speci ici y
100 (% accu acy o he p edic ion low g ade) and diagnos ic accu acy 92.9% (% accu acy o ue p edic ion).
DISSCUSSION
In p esen s udy his ological biopsies we e aken as con ol. Among he included 56 pa ien s wi h u ina y bladde
ca cinoma, we obse ed maximum o 22 cases high g ade muscle in asi e u o helial ca cinoma. High g ade lamina
in asi e u o helial ca cinoma and low-g ade lamina in asi e cases we e epo ed 11 o each. While 12 cases wi h low
g ade supe icial non-in asi e ca cinoma his ologically. The cell su ace glycop o ein CD44 plays a cen al ole in cell o
cell and cell o ma ix adhesion [13]. CD44 p omo es ixa ion and main enance o he issue in eg i y and pa icipa es in
mic oen i onmen al signal ansduc ion [17]. CD44 gene exons can be combined by al e na i e splicing o o m se e al
D . Manoj Kuma Yada e al. Role o CD44 And MMP2 Ma ke in Diagnosis and P ognosis o U ina y Bladde
Ca cinoma. In . J Med. Pha m. Res., 6 (6): 193-200, 2025
198
iso o ms [9]. The CD44 ac s as a me as a ic umou supp esso gene o u ina y bladde ca cinoma [18]. The exp ession o
CD44 bo h a mRNA and p o ein le el is down egula ed du ing bladde cance p og ession, wi h down egula ing high
umou g ade [18].
In p esen s udy based on he ex en and in ensi y o he s aining hey a e di ided in h ee ca ego ies shown in able 1.1d
Table 1.1d CD44 S aining pa e n (memb anous)
Ex en and in ensi y o in ensi y
Sco e
Focally posi i e/Sligh ly he e ogenous s aining
1(Nega i e)
S ong he e ogenous s aining
2 (Posi i e)
S ong homogenous s aining
3 (Posi i e)
MMP2 is a ype o collagenase, 72 kD, which is also known as gela inase and is a membe o o g oup o sec e ed a ying
in size om 110 o 901bp me allop o eases. T MMP2 gene is 17 kb long wi h 12 in ons anging om 175 o 4350bp
loca ed wi hin he egion o ch omosome 16p13.9 [19, 20, 21].
The ex en o s aining was sco ed as % o umou cells posi i e s ained shown in able 1.1e
Table 1.1e MMP2 s aining pa e n (Cy oplasmic)
P opo ion o he umou cell posi i e (%)
Sco e
≤ 25%
1 (Nega i e)
25% - 75%
2(Posi i e)
>75%
3 (Posi i e)
Maximum pa ien s in he p esen s udy we e in hei 50 -80 yea s o age. Bladde ca cinoma was epo ed mo e in male.
Mos o he pa ien s we e p esen ed haema u ia (blood in u ine). Male/Female a io was epo ed 89.3:10.7. Majo
p opo ion o he pa ien s we e diagnosed as high g ade 58.9% (33/56) and 41.1% (23/56) low g ade u o helial ca cinoma
his ologically.
In ou s udy CD44 exp ession was posi i e in 68.18% (15/22) o high g ade muscle in asi e u ina y bladde ca cinoma
which was highe as compa ed o E dogan G. e al [22] and Sugino e al [23]. They epo ed 45% and 33% espec i ely.
Ou s udy epo ed 27% (3/11) high g ade lamina in asi e his inding was signi ican ly low as compa ed o Endogen e al
(45%) and Sugino e al (100%). Howe e , ou s udy epo ed 100% (23/23) posi i i y in in low g ade u o helial ca cinoma
(in asi e o non-in asi e). In his espec inding o ou s udy was exac ly same as compa ed o Endogen e al [22] and
Sugino e . al. [23].
Image-2.1E: CD44 in Low G ade a 100X (Sco e-3). Image-2.1F: CD44 in High G ade a 100X (Sco e-1)
Posi i i y pa e n o MMP2 exp ession (cy oplasmic) in his s udy was epo ed 83.36% (19/22) o high g ade muscle
in asi e ca cinoma i was highe as compa ed o 63% epo ed by E dogan G. e . al. Likewise we ound 100% (11/11) high
g ade lamina in asi e ca cinoma again highe in pe cen age as compa ed o 71% (20/28) epo ed by E dogan G. e . al.
Reason o his di e ence may be a smalle numbe o samples. Low g ade in asi e MMP2 posi i e ca cinoma was ound
36.36% (4/11) which was lowe as compa ed 79% (15/19) epo ed by E dogan G. e . al, again possibili y o a smalle
numbe o samples. Howe e , we epo ed low g ade supe icial MMP2 posi i e ca cinoma 75% (9/12) his alue was
highe in compa ison o 55% (5/9) as epo ed by E dogan G. e . al. Reason o he di e ence may be la ge numbe o
samples.
D . Manoj Kuma Yada e al. Role o CD44 And MMP2 Ma ke in Diagnosis and P ognosis o U ina y Bladde
Ca cinoma. In . J Med. Pha m. Res., 6 (6): 193-200, 2025
199
Image-2.1G: MMP2 Low G ade a 100X (Sco e-1). Image-2.1H: MMP2 Low G ade a 100X (Sco e-3)
Ou s udy esul s ob ain in Indian coho o pa ien is conco dance wi h simila such s udy done wes e n wo ld o coho
s udy. CD44 exp ession is signi ican ly mo e in low g ade non-in asi e u o helial ca cinoma. While MMP2 is signi ican ly
mo e exp essed in high g ade muscle in asi e u o helial ca cinoma.
LIMITATIONS:
Limi a ion o s udy he p esen s udy was su gical p ocedu e TURBT h ough which possibly inadequa e issues we e
ob ained om bladde issue, as i may no ha e all laye s o bladde wall. While Radicle cys ec omy specimens we e may
be pe o med in ad ance s age and hese specimens we e lesse in numbe as compa ed o samples ob ained h oughou
TURBT. Du a ion o s udy was sho e and lesse numbe o samples we e p ocessed.
CONCLUSION
The CD44 exp ession is signi ican ly mo e in low g ade u o helial non muscle in asi e ca cinoma (NMIBC) was ound.
While MMP2 is signi ican ly mo e exp essed in high g ade muscle in asi e u o helial ca cinoma (MIBC). The p edic i e
model as depic ed om ou s udy om he alidi y summa y o logis ic eg ession analysis has shown sensi i i y 89.2%,
speci ici y 100% and diagnos ic accu acy 92.9% ( e able no. 1.1c). I is he e o e, CD44 and MMP2 an ibody ha e a
de ini e ole in he diagnosis and p ognosis o he u ina y bladde ca cinoma as a bioma ke .
Fo de ini e diagnosis and p ognosis, a g ea e numbe o pa ien s wi h long du a ion o ollow up should be done and also
hese inding need o be co ela ed wi h ecen ly desc ibed molecula bioma ke s o u o helial ca cinoma.
CONFLICT OF INTEREST
We decla e no con lic o in e es .
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