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Received 18 September 1999; received in revised form 27 May 2000; accepted 31 May 2000
Abstract
Serum a-N-acetylgalactosaminidase (NaGalase) is responsible for the deglycosylation of vitamin D3-binding protein
(Gc protein). The deglycosylated Gc protein cannot be converted into major macrophage-activating factor (MAF), leading
to immunosuppression. NaGalase is universally detected in a variety of cancer patients, but not in healthy individuals (Cancer
Res. 56 (1997) 28272831). However, the diagnostic/prognostic utility of NaGalase in squamous cell carcinoma (SCC) of the
uterine cervix is not known. To address this issue, the serum NaGalase was quantitatively determined in 210 patients with
different stages of SCC of the uterine cervix. NaGalase levels were increased with the progression of the cancer. After
radiotherapy, the increased levels returned toward or to normal levels in early stages (FIGO stage IIIB) but not in advanced
stages (FIGO stage IIIIV). The present study revealed that the amount of NaGalase in the patient's bloodstream reects the
tumor burden and aggressiveness of the disease. We conclude that NaGalase is an independent predictor of diagnosis/prognosis
in SCC of the uterine cervix, and therefore suggest that quantitative NaGalase alteration may reect important differences in the
immunological functions of these neoplasms. q 2000 Published by Elsevier Science Ireland Ltd. All rights reserved.
Keywords: a-N-Acetylgalactosaminidase; Immunosuppression; Uterine cervix; Squamous cell carcinoma; Macrophage activating factor
1. Introduction
Cervical carcinoma is a major public health
problem in India, as not only the incidence is high
but also because most cases (70%) present themselves
in the advanced stages of the disease at the time of
diagnosis [1]. Cancer patients in the advanced stages,
* Corresponding author. Division of Immunology, Department of
Biotechnology, All India Institute of Medical Sciences, New Delhi
110 029, India. Tel.: 191-11-653-2891; fax: 191-11-685-2286.
E-mail address: vkmalr@hotmail.com (A.L. Reddi).
0304-3835/00/$ - see front matter q 2000 Published by Elsevier Science Ireland Ltd. All rights reserved.
PII: S 0304-383 5(00)00502-4
62
Table 1
Patient's characteristics
Sl. No.
Variable
1.
2.
7.
Menopause status
Pre
Post
160
50
4.
Group I (normal)
85
Group II
FIGO stage
FIGO stage
FIGO stage
FIGO stage
I
II
III
IV
30
73
89
18
Group III
FIGO stage
FIGO stage
FIGO stage
FIGO stage
I
II
III
IV
30
73
89
18
47 (2963)
210
Histological type
Squamous cell carcinoma (SCC)
210
Cervical inltration
.5 mm
5 mm
25
185
Tumor size
.5 cm
5 cm
25
185
6.0) and dialyzed against the same buffer at 48C, overnight. The dialysates were made up to 1 ml with buffer
and assayed for the enzyme activity [6,10]. The
substrate solution (1 ml) contained 5 mmol of p-nitrophenyl N-acetyl-a-d-galactosaminidase in 50 mM
citrate buffer (pH 6.0). The reaction was initiated by
addition of 100 ml of the dialyzed samples kept at
378C for 60 min, and terminated by adding 200 ml
of 10% trichloroacetic acid. After centrifugation of
the reaction mixture, 500 ml of 0.5 M Na2CO3 solution
was added to the supernatant. The amount of p-nitrophenol released was determined spectrophotometrically at 420 nm and expressed as nmol/mg per min
of serum protein. Protein concentrations were determined by the Bradford method [11].
2.2. Statistical analysis
Student's t-test was performed to examine the relationship of the expression of NaGalase in patients
with SCC of the uterine cervix against healthy
controls.
3. Results and discussion
The present study showed increased expression of
NaGalase activity with increasing stages of SCC of the
uterine cervix. Sera of age-matched controls contained
an extremely low level (0.26 ^ 0.1 nmol/mg per min)
of NaGalase (Table 2). NaGalase expression was
63
Table 2
Levels of serum a-N-acetylgalactosaminidase in the SCC of the uterine cervix, before and after radiotherapy a
No. of patients
Group I (normal)
Group II
Stage I
Stage II
Stage III
Stage IV
Group III
Stage I
Stage II
Stage III
Stage IV
a
Range
85
0.26 ^ 0.1
0.180.41
30
73
89
18
0.72 ^ 0.12
1.54 ^ 0.44*
3.78 ^ 1.03**
5.05 ^ 0.17***
0.310.89
0.622.91
1.215.16
3.565.91
30
73
89
18
0.39 ^ 0.08#
0.64 ^ 0.23#
1.38 ^ 0.33##
3.14 ^ 0.86###
0.230.45
0.371.53
0.931.92
2.623.58
*P , 0:05, **P , 0:01, ***P , 0:001 group II vs. group I. #P , 0:05, ##P , 0:01, ###P , 0:001 group III vs. group II.
64
revealed that the levels of NaGalase in the bloodstream reects the tumor burden and aggressiveness
of the disease. A recent experimental study proved
that the amount of NaGalase in the bloodstream is
directly proportional to the number of cancerous
cells or the size of tumor in the hosts [6]. Surgical
removal of malignant lesions resulted in a subtle
decrease in serum NaGalase activity and concomitant
increase in precursor activity. However, even after
surgical removal of tumor lesions, the majority of
postoperative patients carried signicant amounts of
NaGalase activity in their bloodstream, suggesting
that the enzyme is derived from the remnant cancerous lesions and/or metastasized tumor lesions [6]. We
support the recommendation made by Korbelik et al.
[7] that the NaGalase measurement could serve as a
diagnostic and prognostic index that might allow
oncologist to design the dose and the nature of treatment.
Acknowledgements
We thank the Director and Assistant Professors of
Barnard Institute of Radiology and Oncology, General
Hospital, Madras Medical College, Chennai, for
providing blood samples from the cancer patients.
One of the authors Dr A.L. Reddi, thanks the University Grants Commission (UGC), India for nancial
assistance.
References
[1] A.K. Prabhaker, Cervical cancer in India strategy for
control, Int. J. Cancer 29 (1992) 104113.
[2] M. Burnet, Immunological factors in the process of carcinogenesis, Br. Med. Bull. 20 (1964) 154158.