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Evaluation of a new serum tumor marker CYFRA 21.1 for the diagnosis and prognosis of non small cell lung cancer (NSCLL): Preliminary results
40 150
151
PROGNOSTIC VALllE OF THE NEW TUMOR MARKER CZFRA 21-1 IN NON-SMALL CELL LUNG CANCFX. J.Niklihski, M.Furman, E. Chyczewska, L.Chyczewski, F.Rogowski, J.LaudaAski Departments of: Thoracic Surgery, Pneumonology, Pathology and Nuclear Medicine, Medical School, Bialystok, Poland Cytokeratin 19 is particular-y abundant in lung carcinoma. 85 patients (pts) with non-small cell lung cancer- NSCLC (58bperable, 15 unresectable tumors, 12 proved distance metastasis) were investigated to establish CYFRA 21-1 serum utility as a prognostic factor, using IRMA method (CIS bio GIF-SUR-YVETTE).CYFRA 21-1 assays were performed before surgery and serially after tumor resection. In the 73 pts qualified for thoracotomy, increased CYFRA 21-1 levels were observed in 52% (33% of stage I, 47% of stage II, 57% of stage IIIa, 67% of stage IIIb). In 12 pts with TNM IV CYFRA 21-1 elevated levels were obtained in 75% CYFRA 21-1 levels were significantly lower in 58 pts with resectable tumors than in 15 cases with unresectable (p< 0.02). The study proved that CYFRA 21-1 preoperative determination and the course of levels of this marker during follow-up was important. Pretreatment elevation resulted in poorer patient survival. Complete resection resulted in a significant drop in serum CYFRA 21-1 levels in 16 pts who had elevated marker level before surgery and no further disease evidence. In 14 of 58 who survived complete resection, recurrence were subsequently detected. The percentage of recurrence in patients with normal postoperative CYFRA 21-1 levels was 2.3% (l/43). The percentageof recurrence in pts with CYFRA postoperative elevated levels was significantlyhigher and equaled 87% (13/15). In 11 of 13 pts with recurrence after complete resection, recurrent elevation of CYFRA 21-1 preceded changes detectable by CT or clinical examination by 2 to 6 months. In conclusion, CYFRA 21-1 appears to be a useful prognostic marker in NSCLC.
ROLE OF ELASTOTIC FRAMEWORK ON THE TUMOR DEVELOPMENT OF PERIPHERAL LUNG ADENOCARCINOMA LESS THAN 4 CM IN DIAMETER.
T. Eto, H. Suzula, A. Honda,and Y.Nagashima.Shizuoka General Hospital, Shizuoka, Japan. Two hundred six patients of peripheral lung adenocarcinoma (PLA) less than 4 cm in diameter were studied histologically, morphometrically, radiographically and clinicopathologically in special reference to the stromal elastosis. We classified PLA mto two types from the stromal elastotic framework (FFW). Type 1(24 patients) had the preserved EFW consisting of constantly thick stroma. Type 2 (182 patients) revealed the disrupted EFW especially in the center of tumor forming central fibrosis (CF) where many air spaces were collapsed or collagenized. At the periphery of type 2, extending stroma (Exst) was formed with thin walled elastic framework similar to normal alveoli (NA). From the image analysis, increased amounts of elastic fibers could be calculated in type 1 ( 3.3-9.7 fold) and type 2 ( 3.9-7.6 fold) EFW compared to NA, which mean the contraction rate of pre-existing NA. In contrast, Exst in type 2 contained 0.8-2.1 fold of the fibers compared to NA suggesting mild-reacting pre-existing NA. Radiographically, in type 1, tumor size hardly enlarged and the density tended to increase gradually over a long time. In type 2, tumor size tended to increase abruptly over a short time. As prognosis of patients who were followed more than 3 years, 50% had relapsed in type 2, but none in type 1. Conclusion ; Tumor stroma in the early stage of PLA might show the preserved EFW (type 1) formed by contractmg and thickening reaction of NA. As tumor developing, disrupted EFW (type 2) form CF with Exst. It indicate the stromal invasion and directly reflect to the prognosis.
153
152 EVALUATION
OF
A
NEW
21.1 FOR THE DIAGNOSIS
SERUM TUMOR MARKER CYFRA
AND PROGNOSIS OF NON SMALL CELL LUNG CANCER (NSCLL) PRELIMINARY RESULTS. JM. Br&hot*, J.Nataf**, J.F&ult**, MF.D&*, B. Tbirion***, J.Miltgen*, J. Rochemaure* - * Service de F’neumologie, ** Labaatoire Biophysique, H&lDia. 75004 PARIS. **I* L.abomtoire Cis-Bio intemational. m : Analysis of swum CYFRA 21.1 concentrations before. and after
:
treatment in NSCLC patients (pts), accordiig to histology, TNM, response to treatment and overall survival. Me&& Prospective study with measure by immumradiometric assay of smun concentrations of CYFRA 21.1, carcincembryonic antigen (CEA), squamous cell carcinoma antigen @CC), CA 125, CA 19.9, neumn-specific an&se (NSE) in resectableand umesectable NSCLC. I&!&:
:_
: ; 3 stage
;
w 7 pts (6 M ,1 F) 2 squamous cell (SC) carcinoma, 5 adenowcinomn (ADC) I, 2 stage II, 2 stage mA; Cylia 21-I > 3,6 ng/ml in 1 (with stage I SC carcinoma) before resection and normal after resection. GrwwII:22pts(13M,9F);llSC carcinoma, 7 ADC, 3 large cell carcinoma
;
(LCC), 1 composite (SC + small cell carcinoma) 9 stage III B, 12 stage IV, 1 stage (I). Cyiin21.1 elevatedin 13 (mean 24.1, 4.0 to 89) S/l1 SC carcinoma, 317 ADC, 2i3 LCC ; SCC elevated in 4 out of 22, always associated to ao atmormal value of Cyfm 21.1 ofserumvalue ofCyfra21.1 in the 3 Pa&l Responses, in 1 Stable Disease, in 1 Progression elevation in 1 Stable Disease and 2 Pmpssion. Conclusion preliminary study, - Cytia21.1 serumconcentmtionsarealmcwmal in9/13 SC c~~cmoma, 3/12ADC, 213 LCC. - Abnormal values of Cyiia 21.1 are more Erequently observed in advanced NSCLC (l/7 resectable pts. 1302 unresectable pts). - There is a dramatically decrease of Cyfra 21 .l ccmcentralions in the 3 responders and in the resectable patient. The study is on-going.
; reduction
: Inthis
:
; seccmdary
CHRONIC
INHALATION
MUl_TlF‘!CAL
OF
URBAN
AMBIENT
NEUROENWCRlNE
HYPERPLASIA
IN
M.
Kanisawa,
Y.
lnayama.
THE
CELL
RAT
AIRWAY
T. Shibagaki, wept. Path&,
still
uncertain
model.
This
ambient and
paper
air
induces
H. Kitamurrr. TYokohama City
facilities tow”
in
installed
university during
of the
78
by in
in
in
the
the
serial
to
mostly
exposed these
for
between the
urban derived of
the
contents ambient from
pulmonary
exposed
inhaled of
air
dust air
the for
78
densely
automobile neurcendacrine
polluted exhaust cell
of
lated
observed
was
may
the
cells
reaction peptide
adenocarcinoma
dust be
may
wz
difference
detected
results
tumor
atypical
of
positive
with gas
52
particular-
“umber
of
26,
multiple
Significant
groups These
the
examined
frequently
genera type
weeks.
in both
recorded
foci
showed
the
air.
bronchioli, were
usual
particles.
of and
calcitonine
of
in
at
were
Certain
lesion
to
Development in 2 rats
in the region
neoplastic
were
lungs
bronchi
7X weeks.
in down-
bred
sacrificed
Production
small
found
immtntohistochemically found
particles the
sections.
mid
traffic were
male
animal
Hepa-filtered
were
and
brcnchio~oalveoIar
rat
composing (CGRP).
dust
weeks
the
hyperplasia
ly
axl
Animals
experimental
papiliomas cell
SOz
gas
PapillOmaS Sixty-six
heavy
is supplied
urban
in the
rats
cancer
exhaust cell
air
with
lung
of
animal
Of
epithelium.
pollutd control
facilities
NOX.
histogically
airway
a street
experment.
cell
neuroendocrine
Nontreated
aimal
Densities
inhalation
to
AND
Schwa1
proper
automobile
rat
on
Yokohama.
and
the
exposed
the
with
of
It% Univ.
smal1
of
chronic
polluted
were
of
lacking
incidence
hyperplasia rats
to
reports
chiefly
a high
Wistar
due
INDU=s
EF’ITHELIUM.
Medicine, Yokdaama, Japan. The real cause and pathogenesis are
AIR
PAF’ILLOMAS
only
in
suggest
particles a possible
in human.
cause
151
PROGNOSTIC VALllE OF THE NEW TUMOR MARKER CZFRA 21-1 IN NON-SMALL CELL LUNG CANCFX. J.Niklihski, M.Furman, E. Chyczewska, L.Chyczewski, F.Rogowski, J.LaudaAski Departments of: Thoracic Surgery, Pneumonology, Pathology and Nuclear Medicine, Medical School, Bialystok, Poland Cytokeratin 19 is particular-y abundant in lung carcinoma. 85 patients (pts) with non-small cell lung cancer- NSCLC (58bperable, 15 unresectable tumors, 12 proved distance metastasis) were investigated to establish CYFRA 21-1 serum utility as a prognostic factor, using IRMA method (CIS bio GIF-SUR-YVETTE).CYFRA 21-1 assays were performed before surgery and serially after tumor resection. In the 73 pts qualified for thoracotomy, increased CYFRA 21-1 levels were observed in 52% (33% of stage I, 47% of stage II, 57% of stage IIIa, 67% of stage IIIb). In 12 pts with TNM IV CYFRA 21-1 elevated levels were obtained in 75% CYFRA 21-1 levels were significantly lower in 58 pts with resectable tumors than in 15 cases with unresectable (p< 0.02). The study proved that CYFRA 21-1 preoperative determination and the course of levels of this marker during follow-up was important. Pretreatment elevation resulted in poorer patient survival. Complete resection resulted in a significant drop in serum CYFRA 21-1 levels in 16 pts who had elevated marker level before surgery and no further disease evidence. In 14 of 58 who survived complete resection, recurrence were subsequently detected. The percentage of recurrence in patients with normal postoperative CYFRA 21-1 levels was 2.3% (l/43). The percentageof recurrence in pts with CYFRA postoperative elevated levels was significantlyhigher and equaled 87% (13/15). In 11 of 13 pts with recurrence after complete resection, recurrent elevation of CYFRA 21-1 preceded changes detectable by CT or clinical examination by 2 to 6 months. In conclusion, CYFRA 21-1 appears to be a useful prognostic marker in NSCLC.
ROLE OF ELASTOTIC FRAMEWORK ON THE TUMOR DEVELOPMENT OF PERIPHERAL LUNG ADENOCARCINOMA LESS THAN 4 CM IN DIAMETER.
T. Eto, H. Suzula, A. Honda,and Y.Nagashima.Shizuoka General Hospital, Shizuoka, Japan. Two hundred six patients of peripheral lung adenocarcinoma (PLA) less than 4 cm in diameter were studied histologically, morphometrically, radiographically and clinicopathologically in special reference to the stromal elastosis. We classified PLA mto two types from the stromal elastotic framework (FFW). Type 1(24 patients) had the preserved EFW consisting of constantly thick stroma. Type 2 (182 patients) revealed the disrupted EFW especially in the center of tumor forming central fibrosis (CF) where many air spaces were collapsed or collagenized. At the periphery of type 2, extending stroma (Exst) was formed with thin walled elastic framework similar to normal alveoli (NA). From the image analysis, increased amounts of elastic fibers could be calculated in type 1 ( 3.3-9.7 fold) and type 2 ( 3.9-7.6 fold) EFW compared to NA, which mean the contraction rate of pre-existing NA. In contrast, Exst in type 2 contained 0.8-2.1 fold of the fibers compared to NA suggesting mild-reacting pre-existing NA. Radiographically, in type 1, tumor size hardly enlarged and the density tended to increase gradually over a long time. In type 2, tumor size tended to increase abruptly over a short time. As prognosis of patients who were followed more than 3 years, 50% had relapsed in type 2, but none in type 1. Conclusion ; Tumor stroma in the early stage of PLA might show the preserved EFW (type 1) formed by contractmg and thickening reaction of NA. As tumor developing, disrupted EFW (type 2) form CF with Exst. It indicate the stromal invasion and directly reflect to the prognosis.
153
152 EVALUATION
OF
A
NEW
21.1 FOR THE DIAGNOSIS
SERUM TUMOR MARKER CYFRA
AND PROGNOSIS OF NON SMALL CELL LUNG CANCER (NSCLL) PRELIMINARY RESULTS. JM. Br&hot*, J.Nataf**, J.F&ult**, MF.D&*, B. Tbirion***, J.Miltgen*, J. Rochemaure* - * Service de F’neumologie, ** Labaatoire Biophysique, H&lDia. 75004 PARIS. **I* L.abomtoire Cis-Bio intemational. m : Analysis of swum CYFRA 21.1 concentrations before. and after
:
treatment in NSCLC patients (pts), accordiig to histology, TNM, response to treatment and overall survival. Me&& Prospective study with measure by immumradiometric assay of smun concentrations of CYFRA 21.1, carcincembryonic antigen (CEA), squamous cell carcinoma antigen @CC), CA 125, CA 19.9, neumn-specific an&se (NSE) in resectableand umesectable NSCLC. I&!&:
:_
: ; 3 stage
;
w 7 pts (6 M ,1 F) 2 squamous cell (SC) carcinoma, 5 adenowcinomn (ADC) I, 2 stage II, 2 stage mA; Cylia 21-I > 3,6 ng/ml in 1 (with stage I SC carcinoma) before resection and normal after resection. GrwwII:22pts(13M,9F);llSC carcinoma, 7 ADC, 3 large cell carcinoma
;
(LCC), 1 composite (SC + small cell carcinoma) 9 stage III B, 12 stage IV, 1 stage (I). Cyiin21.1 elevatedin 13 (mean 24.1, 4.0 to 89) S/l1 SC carcinoma, 317 ADC, 2i3 LCC ; SCC elevated in 4 out of 22, always associated to ao atmormal value of Cyfm 21.1 ofserumvalue ofCyfra21.1 in the 3 Pa&l Responses, in 1 Stable Disease, in 1 Progression elevation in 1 Stable Disease and 2 Pmpssion. Conclusion preliminary study, - Cytia21.1 serumconcentmtionsarealmcwmal in9/13 SC c~~cmoma, 3/12ADC, 213 LCC. - Abnormal values of Cyiia 21.1 are more Erequently observed in advanced NSCLC (l/7 resectable pts. 1302 unresectable pts). - There is a dramatically decrease of Cyfra 21 .l ccmcentralions in the 3 responders and in the resectable patient. The study is on-going.
; reduction
: Inthis
:
; seccmdary
CHRONIC
INHALATION
MUl_TlF‘!CAL
OF
URBAN
AMBIENT
NEUROENWCRlNE
HYPERPLASIA
IN
M.
Kanisawa,
Y.
lnayama.
THE
CELL
RAT
AIRWAY
T. Shibagaki, wept. Path&,
still
uncertain
model.
This
ambient and
paper
air
induces
H. Kitamurrr. TYokohama City
facilities tow”
in
installed
university during
of the
78
by in
in
in
the
the
serial
to
mostly
exposed these
for
between the
urban derived of
the
contents ambient from
pulmonary
exposed
inhaled of
air
dust air
the for
78
densely
automobile neurcendacrine
polluted exhaust cell
of
lated
observed
was
may
the
cells
reaction peptide
adenocarcinoma
dust be
may
wz
difference
detected
results
tumor
atypical
of
positive
with gas
52
particular-
“umber
of
26,
multiple
Significant
groups These
the
examined
frequently
genera type
weeks.
in both
recorded
foci
showed
the
air.
bronchioli, were
usual
particles.
of and
calcitonine
of
in
at
were
Certain
lesion
to
Development in 2 rats
in the region
neoplastic
were
lungs
bronchi
7X weeks.
in down-
bred
sacrificed
Production
small
found
immtntohistochemically found
particles the
sections.
mid
traffic were
male
animal
Hepa-filtered
were
and
brcnchio~oalveoIar
rat
composing (CGRP).
dust
weeks
the
hyperplasia
ly
axl
Animals
experimental
papiliomas cell
SOz
gas
PapillOmaS Sixty-six
heavy
is supplied
urban
in the
rats
cancer
exhaust cell
air
with
lung
of
animal
Of
epithelium.
pollutd control
facilities
NOX.
histogically
airway
a street
experment.
cell
neuroendocrine
Nontreated
aimal
Densities
inhalation
to
AND
Schwa1
proper
automobile
rat
on
Yokohama.
and
the
exposed
the
with
of
It% Univ.
smal1
of
chronic
polluted
were
of
lacking
incidence
hyperplasia rats
to
reports
chiefly
a high
Wistar
due
INDU=s
EF’ITHELIUM.
Medicine, Yokdaama, Japan. The real cause and pathogenesis are
AIR
PAF’ILLOMAS
only
in
suggest
particles a possible
in human.
cause