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Rearrangement Supports a True Natural Killer-Cell Lineage in a Subset of Sinonasal Lymphomas
From the Department of Pathology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
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Abstract |
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 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
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rearrangement pattern, expressed another NK cell
receptor, NKG2a, and were usually CD56-positve,
cyclin-dependent kinase-6 (CDK6)-positive,
CD44-negative, a phenotype already reported to indicate a true
NK cell lineage. We conclude that, although sinonasal lymphomas
have heterogeneous genotypes and phenotypes, a restricted KIR
repertoire without TCR- rearrangement provides preliminary support
for the monoclonality hypothesis and can be used for defining a true
NK-cell lineage in a subset of sinonasal lymphomas.
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Introduction |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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Despite the well-characterized angiocentric histopathology, the origin of this lymphoma remains controversial. The lymphoma often expresses a NK-cell marker, CD56, and some T-cell-related antigens such as CD2, CD43, and/or CD45RO. However, it lacks other T-lineage antigens, such as CD4, CD5, CD8, and surface CD3, and rarely has a T-cell-receptor gene rearrangement (TCR-GR).3,4 The ambiguous phenotype partially reflects the fact that NK cells are developmentally close to T cells, both possibly arising from a bipotent T/NK progenitor.5-8 Consequently, the lymphoma was simply designated as angiocentric lymphoma in the REAL (revised European American lymphoma) classification, without further specification of its cellular origin, T- or NK-cell.
After the REAL classification, attempts have been made to separate nasal lymphoma of true NK-cell lineage from that of T-cell lineage. For example, it was concluded that lymphomas with expression of CD56 and CD3e, lack of CD5, and without TCR-GR were of NK lineage.3,9 Recently, we demonstrated that nuclear expression of cyclin-dependent kinase-6 and surface loss of CD44 without TCR-GR favor a true NK-cell nasal lymphoma.10
NK cells use both killer cell immunoglobulin-like receptors (KIRs) and C-type lectin receptors (NKG2) to recognize major histocompatibility complex class I molecules on autologous cells.11 The receptor-major histocompatibility complex binding delivers an inhibitory signal and protects autologous cells from NK-mediated cytotoxicity. Whenever NK cells interact with a target cell without major histocompatibility complex class I molecules as a result of viral infection or tumor transformation, a cytotoxic effect is initiated, leading to destruction of the target cells.12,13 Despite the very important immunological functions of these receptors, very limited data are available on the status of their expression in lymphomas.
It is known that expression of NKG2 is susceptible to interleukin (IL)-15 regulation.14 A recent report also demonstrated NKG2A expression in each of four cases of sinonasal lymphoma, but rarely in lymphomas of T- or B-cell origin.15 NKG2A thus seems to be a marker for sinonasal lymphoma. However, its use as a marker for lineage or monoclonality assignment has yet to be determined.
It is already known that the KIR receptors belong to 12 families, that each NK cell displays, on average, 3 to 4 families of KIRs, and that most people have a KIR repertoire of 6 to 9 KIR families.16,17 Therefore, a monoclonal population derived from a single NK cell would have a KIR repertoire restricted to three to four families. In contrast, a polyclonal NK-cell population would display an unrestricted distribution of the KIR repertoire covering six to nine families. Because the rationale of NK-cell repertoire restriction in a monoclonal or an oligoclonal NK-cell population is similar to the phenomenon of light-chain restriction in B-cell lymphoma, we proposed to use a restricted NK-cell repertoire as a criterion for assigning a sinonasal lymphoma to the NK lineage.
To obtain a simple experimental design, we noticed that the 12 families share a consensus sequence composed of three immunoglobulin (Ig)-like domains.18 By sequence analysis, the 12 families can be broadly divided into three groups, 2DL4, 2D, and 3D, that differ in the constituent domains. Group 2DL4 has the first and the third domains, group 2D has the second and the third domains, and group 3D has all three domains.18 If the KIR repertoire from a sinonasal lymphoma can be shown to be composed of only one or two of the three groups, then a restricted pattern is demonstrated, and a monoclonal NK-cell nature can be confirmed.
Based on these observations, we believe that a restricted KIR repertoire is a marker for NK cell differentiation. To exclude the less likely event, in which KIR might be expressed by a minor subset of T cells, we propose that a restricted KIR repertoire without T-cell receptor rearrangement could be used for assigning a subset of sinonasal lymphoma to a true NK cell lineage.
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Materials and Methods |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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Ten cases of lymphoma of the nasal cavity and paranasal sinuses were diagnosed in the Pathology Department of the National Taiwan University Hospital between 1993 and 1999. The diagnosis was made initially by a combination of morphology and immunohistochemistry. All 10 cases were CD3-positive or CD45RO-positive by immunohistochemistry. At the time of diagnosis none of the patients had lymphoma involvement outside the nasal cavity or the adjacent paranasal sinuses. In addition, 10 cases of T-cell lymphoma and 10 cases of reactive conditions involving T/NK cells were used as controls. The reactive controls included hyperplastic tonsils, lymph nodes with T-zone expansions, B-cell lymphomas, mononuclear cells from normal peripheral blood, and gestational endometrium. The last type of tissue was chosen because of its known unrestricted KIR repertoire.19,20
RNA Extraction
RNA was extracted from formalin-fixed, paraffin-embedded tissue by the Trizol method. Briefly, a 20- to 60-µm section of the tumor was mixed with 1 ml of xylene for 2 minutes for removal of paraffin. After centrifugation, residual xylene was dissolved in ethanol and removed by evaporation. The deparaffinized tissue was mixed with 180 µl of lysis buffer and 20 µl of proteinase K at 55°C overnight. Then 1 ml of Trizol (phenol/guanidine isothiocyanate) and 0.2 ml of chloroform were added. After vortexing and centrifugation, the aqueous phase containing RNA was saved. The RNA was precipitated by isopropanol and redissolved in diethyl pyrocarbonate-treated water for future use.
Group-Specific Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) for KIR
The nucleotide sequences for human KIR have been
published.18
The KIR transcripts have a consensus
structure containing a leader sequence followed by three Ig-like
domains. The first domain extends from nucleotide 106 to nucleotide
391, the second domain from nucleotide 392 to nucleotide 691, and the
third domain starts from nucleotide 692 (Figure 1)
. Probably because of alternative
splicing, group 2DL4 skips the second domain,
group 2D skips the first domain, and group 3D retains both domains.
Hence, group 2DL4 has a unique junction between
the first and the third domains, group 2D has a unique junction between
the leader sequence and the second domain, and group 3D has a unique
junction between the first and second domains.
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and Figure 1
). For example, the pairs
341 to 363 and 700 to 723 can amplify group 2DL4
to yield a specific PCR product with 83 nucleotides. Although a second
product of 383 nucleotides because of nonspecific hybridization to
group 3D is theoretically possible, this product can easily be
separated by electrophoresis, and is not detected in our system,
presumably because the much larger size makes its RT-PCR inefficient.
Similarly, the pairs 61 to 85 and 406 to 430 are group 2D-specific, and
they yield a PCR product of 85 nucleotides. Finally, the pairs 341 to
363 and 406 to 430 placed at the first and the second domains can
amplify group 3D specifically, because it is the only transcript
containing both domains. The PCR product has 90 nucleotides.
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One-tenth of the reaction mixture was used for PCR. The 20-µl PCR
reaction mixture included 50 mmol/L Tris-HCl, pH 9.1, 3.5 mmol/L
MgCl2, 16 mmol/L ammonium sulfate, 150 µg/ml
bovine serum albumin, 200 µmol/L of each dNTP, 2 µmol/L
[TAMRA]-dCTP, 0.3 µmol/L of each primer set, and 1 U of
Taq polymerase. Each cycle consisted of denaturation at
94°C for 45 seconds, annealing at 40°C for 45 seconds, and
extension at 72°C for 45 seconds. The PCR reaction was performed for
35 cycles. At the end of the 35 cycles, a portion of the PCR products
was loaded and separated by a DNA analyzer (ABI377 with GeneScan
software; Perkin-Elmer, Foster City, CA). A typical result is shown in
Figure 2
.
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. If the peak was indistinguishable from
background, a minus sign was entered in Table 2
.
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RT-PCR for NKG2A was done with the primers 5'-ATAGATAATGAAGAAGAAAT-3' (633 to 652) and 5'-CATTGTCACCCATGGATGATG-3' (731 to 711). The numbers in parentheses are the nucleotide positions of the RNA transcript. The RT-PCR conditions used and the analysis of the data were the same as those for the RT-PCR for KIR.
DNA Extraction
Genomic DNA was extracted from paraffin-embedded tissue blocks by use of a QIAamp kit (Qiagen, Valencia, CA). Briefly, a 20- to 60-µm section was mixed with 1 ml of xylene at room temperature for 2 minutes for removal of paraffin. After centrifugation, residual xylene was dissolved in ethanol and removed by evaporation. The deparaffinized tissue was mixed with 180 µl of lysis buffer and 20 µl of proteinase K at 55°C overnight. After centrifugation, the supernatant containing DNA was saved. The DNA was precipitated by ethanol and redissolved in Tris-ethylenediaminetetraacetic acid buffer for future use.
T-Cell-Receptor Gene Rearrangement
The TCR--chain gene was examined by multiplex nested
PCR, as modified from a previous report.22
In the first
multiplex PCR, four primers, VrI, VrII, VrIII, and VrIV, were used to
anneal to the variable regions of TCR-, and three
primers, Jr1/2, Jpr, and Jpr1/2, were used to anneal to the junctional
regions of the TCR-. The primer sequences were as
follows: VrI, 5'-TACATCCACTGGTACCTACACCAG-3'; VrII,
5'-GAAAGGAATCTGGCATTCCG-3'; VrIII, 5'-AAGCAACAAAGTGGAGGCAAGAAAG-3';
VrIV, 5'-CTCACACTCTCACTTC-3'; Jr1/2, 5'-CAAGTGTTGTTCCACTGCC-3'; Jpr,
5'-TTGTTCCGGGACCAAATACC-3'; and Jpr1/2, 5'-GTTACTATGAGCCTAGTC-3'.
In the second nested PCR, we used primers V,
5'-TCTGGAGTCTATTACTGTGC-3', and Jr,
5'-(6-FAM)-AGTGTAGTCCCTGTACCAAACATTTT-3', to anneal to the consensus
regions of the variable and junctional regions of TCR-.
Each 20-µl reaction mixture contained 50 mmol/L Tris-HCl, pH 9.1, 3.5
mmol/L MgCl2, 16 mmol/L ammonium sulfate, 150
µg/ml bovine serum albumin, 200 µmol/L of each dNTP, 0.3 µmol/L
of each primer set, 2 µl of DNA from the first PCR reaction, and 1 U
of Taq polymerase. The reaction mixture was subjected to 35
cycles of PCR after an initial 2-minute denaturation step at 94°C.
Each cycle consisted of denaturation at 94°C for 45 seconds,
annealing at 40°C for 45 seconds, and extension at 72°C for 45
seconds. At the end of 35 cycles, a portion of the PCR product was
loaded on and separated by a DNA analyzer (ABI377 equipped with
GeneScan software, Perkin-Elmer). A typical result is shown in
Figure 3
.
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Immunohistochemistry was done according to a protocol published
from our laboratory.10
Briefly, immunostaining for cdk6
was performed with an affinity-purified rabbit polyclonal antibody that
recognized a peptide corresponding to amino acid residues 306 to 326
mapping at the carboxyl terminus of cdk6 (C-21 antibody; Santa Cruz
Biotechnology, Santa Cruz, CA). Immunostaining for CD44 was performed
with a monoclonal antibody, anti-human CD44H (2C5/IgG2a subclass; R&D
Systems Ltd., Minneapolis, IN), that recognized all CD44 isoforms,
including the standard CD44 isoform (CD44s). Additional antibodies,
CD3
(polyclonal) or CD45RO (DAKO SA, Glostrup, Denmark), and CD56
(Novocastra Lab Ltd., Newcastle, UK), were used according to the
manufacturer’s recommendation.
Quantitative evaluation of cdk6 expression was performed by counting of the percentage of positively stained cells in high-power (x40) microscopic fields.10 The percentages of tumor cells expressing nuclear cdk6 were defined as follows: -, <10%; +, 10 to 30%; ++, 30 to 50%; and +++, 50 to 100%.
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Results |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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The series of sinonasal T/NK cell lymphomas included 10 male
patients with an age distribution from 24 to 67 years. All initially
had disease localized to the sinonasal area. Biopsies were taken before
initiation of chemotherapy or radiation therapy, and they were
classified histologically as pleomorphic medium- and large-cell
lymphoma. Coagulative necrosis was seen in nearly all of these cases.
Angioinvasion was present to variable degrees. All 10 cases were
CD3-positive or CD45RO (UCHL-1)-positive, and most of them were
CD56-positive by immunohistochemistry (Table 2)
. In situ
hybridization for EBV was positive in all cases. The immunophenotypes
of these 10 cases were included in our previous
publication.10
The male predominance and the pathology
findings are consistent with other previous reports.1,2,
KIR Repertoire by Group-Specific RT-PCR
The RT-PCR approach for characterizing the KIR repertoire is well
established, and was shown to correlate well with surface expression of
KIR receptors.16,17
For the present study, we modified and
developed a group-specific RT-PCR for KIR by amplifying the unique
junction that is present only in one of the three groups. A schematic
presentation for this approach is shown in Figure 1
. The PCR product
was then separated by a high-resolution polyacrylamide system, the
GeneScan, a typical result of which is shown in Figure 2
.
If any one of the three group-specific RT-PCRs yielded a peak, then a
KIR repertoire was detected, and the relative sizes of the three peaks
were entered in Table 2
. If the sizes of the three peaks were all
indistinguishable from baseline fluctuations, a minus sign was entered
in Table 2
. In our system, a peak would become undetectable if it was
equal to or less than 1% of the size of the actin peak.
Most sinonasal lymphomas listed in Table 2
had a detectable KIR
repertoire (9 of 10). The relative proportions of the three groups of
KIR transcripts were shown, and it is apparent that the KIR repertoires
for all nine cases were restricted to one or two groups, consistent
with monoclonal NK cell proliferation. One case did not have detectable
KIR transcripts. Although accidental degradation of RNA and extensive
necrosis of the tissue might have caused a false-negative result, this
particular case seemed to be true negative, as RT-PCR for ß-actin and
NKG2A were both positive and served as internal positive controls.
The majority of T-cell lymphomas were negative for KIR (8 of 10), as predicted, but two cases were KIR-positive. Expression of KIR in these two peripheral T-cell lymphomas could be false-positive, or they might represent lymphomas arising from a minor subset of T cells that normally expressed KIR. Although we could not distinguish between the two possibilities, the data showed that a KIR repertoire is much more likely to be associated with a sinonasal lymphoma than with a T-cell lymphoma, and can be used to define a NK-cell lineage in sinonasal lymphomas.
Measurements of the KIR repertoire were done on 10 additional cases of
reactive T/NK proliferation. These included two hyperplastic tonsils,
two lymph nodes with T-zone hyperplasia, two B-cell lymphomas,
mononuclear cells from the peripheral blood of two healthy normal
patients, and two gestational endometrial biopsy specimens. An
unrestricted pattern of KIR repertoire was found, as expected, from the
endometrium and peripheral blood. The hyperplastic tonsils, lymph nodes
with T-zone hyperplasia, and one B-cell lymphoma showed no detectable
KIR repertoires, which simply meant that the NK cells in the specimens
were below the detection limit of our measurement system. The absence
of a KIR repertoire in tonsils is consistent with a previous report
that the number of NK cells in acute tonsillitis or hypertrophic
tonsils is only 
1%,23
which is about the detection
limit of our system. Interestingly, the second B-cell lymphoma showed a
restricted pattern of KIR repertoire. The intensities of KIR
transcripts in this case were weak and should be because of
infiltrating NK cells reactive to the B-cell lymphoma, but the cause
for the restriction deserves further investigation. The KIR repertoire
of case 9 was very disturbed because of a low percentage of
KIR2DL4 at 2%, which was confirmed by a repeated
measurement. This also raised the possibility of monoclonal NK mixed
with some reactive NK cells. Although some of these possibilities could
not be resolved, the data did show that most reactive conditions had
either no KIR repertoires or unrestricted KIR repertoires, and gave
further support to the use of restricted KIR repertoires as markers for
sinonasal lymphomas.
RT-PCR for NKG2A
We also used RT-PCR to determine NKG2A transcript in sinonasal lymphoma, and we identified its presence in most cases (9 of 10), but only rarely in T-cell lymphomas (2 of 10). For the reactive controls, NKG2A was positive in the endometrium and peripheral blood, but was not found in B-cell lymphoma, hyperplastic tonsils, or lymph nodes with T-zone expansion. The result is consistent with a previous report that four out of four cases of sinonasal lymphoma had NKG2A expression by immunohistochemistry, but this expression was rarely found in other T- or B-cell lymphomas.15
TCR- Gene Rearrangement
A PCR-based TCR--GR study was performed
according to a previously published protocol, with slight
modifications.22
The PCR products were separated by the
GeneScan system, a typical result of which is shown in Figure 3
. The
data for all of the cases are listed in Table 2
. We found that most
sinonasal lymphomas did not have monoclonal
TCR- rearrangement (7 of 10) and most T-cell
lymphomas were monoclonal (7 of 10). However, there were three cases of
sinonasal lymphoma with monoclonal TCR rearrangement and three cases of
T-cell lymphoma without TCR rearrangement. The three T-cell lymphomas
without a monoclonal TCR--GR were false-negative because
monoclonality could be shown by either TCR-ß rearrangement or
cytogenetics. As for the three sinonasal lymphomas with monoclonal
TCR--GR, it is less clear whether they were
true or false-positive. Because KIR could be found rarely on a minor
subset of T cells, a lymphoid tumor cell might simultaneously express
KIR and rearrange TCR.
Immunophenotype
We performed immunostaining for CD3, CD56, CDK6, and CD44. A
typical result is shown in Figure 4
.
Sinonasal lymphomas are usually CD3+ and CD56+, and peripheral T-cell
lymphomas are usually CD3+ and CD56-. Sinonasal lymphomas have strong
nuclear expression of CDK6, but frequent loss of surface CD44, and
peripheral T-cell lymphomas are usually CDK6-negative but usually
CD44-positive. The two cases of lymphoblastic lymphoma had strong
expression of CDK6, which is also consistent with previous
reports.24
The immunophenotyping provides an independent
criterion for lineage assignment, and is approximately consistent with
lineage assignment based on consideration of KIR repertoires and
TCR rearrangements.
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Sinonasal lymphoma seems, as shown in Table 2
, to be heterogeneous
both genotypically and phenotypically, and cannot be completely
separated from peripheral T-cell lymphomas by any single marker.
However, the expression of KIR correlates fairly well with the
expression of NKG2a, CD56, and CDK6, and the absence of CD44, and is
about as good as the other markers in distinguishing sinonasal
lymphomas from peripheral T-cell lymphomas.
We therefore propose to use restriction of the KIR repertoire without
TCR- rearrangement as a criterion for a true NK cell
lineage. When the criterion was applied to the 10 cases listed in Table 2
, 6 cases could be assigned to the true NK lineage. Three cases had
both KIR expression and TCR- rearrangement, which
probably represents dual differentiations toward both T and NK
lineages, although a false-positive TCR-
rearrangement could not be excluded completely. The lineage in
the remaining one case without TCR- rearrangement or KIR
expression is undetermined.
When the same principle was applied to two lymphoblastic
lymphomas and eight peripheral T-cell lymphomas, we found that the two
lymphoblastic lymphomas and four of the eight peripheral T-cell
lymphomas had TCR- rearrangement without KIR expression,
consistent with a T lineage. Cases 3 and 6 did not have monoclonal
TCR- rearrangement and did not express KIR. The lineage
was undetermined. Case 9 expressed KIR without a monoclonal
TCR- rearrangement, consistent with an NK-cell lineage.
Case 10 showed both TCR- rearrangement and KIR
expression, consistent with dual differentiation. Case 6 would have a
T-lineage and case 9 a lineage of dual differentiation, if we also
considered the status of TCR-ß rearrangement. Apparently
the test was limited by the low sensitivity for detecting
TCR- rearrangement, that led to wrong assignments in two
cases.
Correlation with Morphology and Response to Chemotherapy and Clinical Outcome
We were unable to find significant morphological differences between the KIR+ and KIR- cases. There seemed to be no correlation between the clinical course and the status of KIR repertoires. A larger sample size and a longer follow-up might be necessary for a significant conclusion.
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Discussion |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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Monoclonality is probably the single most important test in
hematopathology. The classical example is the light-chain restriction
in B-cell neoplasms. The rationale for the KIR repertoire restriction
is similar to that of light-chain restriction. However, experimentally
it is more complicated because each NK cell can express 3 or 4 KIRs out
of 12 families, whereas each B cell displays either 
or 
light
chain.16,17
To simplify the experiments, we took advantage
of the fact that the 12 families share sequence homology and could be
divided into three groups.18
By group-specific or
junction-specific RT-PCR, we demonstrated that, in sinonasal lymphoma,
a restricted pattern could be identified in all nine cases with a KIR
repertoire.
Strictly speaking, a restricted pattern may be because of a monoclonal or oligoclonal NK proliferation. Further experimental data would be required for finding out how common it is to have an oligoclonal NK proliferation, and how important it is to distinguish between this condition and a true monoclonal proliferation. Similarly, more data would be required for determining whether other NK-cell neoplasms also have restricted KIR repertoires.
Regardless of these limitations, we can use the status of the KIR
repertoire restriction in conjunction with TCR--GR to
achieve a lineage assignment for sinonasal lymphoma. We find six cases
with true NK cell differentiation, three cases with probable dual T/NK
differentiation, and one case with no differentiation. This reflects
the current model of T- and NK-cell development, in which a common
lymphoid precursor gives rise to a bipotent T/NK progenitor, which
subsequently develops into T and true NK cells.28-30
Extensive characterization of the KIR and NKG2 repertoire of normal NK cells in peripheral blood has been reported.16,17 It has been established that the RT-PCR approach to mRNA transcripts gives the same result as does immunocytochemical staining of surface receptors.16,17 However, only limited data are available on surface KIR and NKG2 expression in sinonasal lymphoma. In the only report based on immunohistochemical staining, each of four cases stained positively for NKG2A, but only one of four cases stained positively for KIR.15 Taking the small sample sizes into consideration, the data of Haedicke and colleagues15 are approximately consistent with the present report that 9 of 10 cases were positive for NKG2A. We, therefore, agree with the view that NKG2A is a general marker in sinonasal lymphoma. In contrast, we found a higher frequency of KIR positive cases (nine of ten). Although multiple antibodies were used in the previous study, the failure to detect KIR raised the possibility of false negativity. Because RT-PCR is more sensitive than immunostaining, the increased sensitivity might account for the discrepancy.
Sinonasal lymphoma is usually TCR--GR-negative, but our
data show that some cases (3 of 10) had a monoclonal
TCR--GR. Although a false-positive result could not be
completely excluded, the monoclonal rearrangement might be true,
considering that we used the GeneScan system, which offered a higher
resolution than did the agarose gels used in previous studies,
including ours.10
The finding of monoclonal
TCR--GR in sinonasal lymphoma is in consistent with a
recent publication that demonstrated both NK-cell and gamma-delta
T-cell lines established from primary lesions of nasal T/NK-cell
lymphomas associated with the Epstein-Barr virus.31
On the
other hand, we unexpectedly found two KIR-positive T-cell lymphomas.
Whether these are false-positive or represent dual differentiation
requires further investigation. Taken together, our data showed that
most sinonasal lymphomas belong to the true NK cell lineage, 7 of 10
T-cell lymphomas belong to the T-lineage if the status of
TCR-ß rearrangement was also considered, and a minority of
sinonasal or T-cell lymphomas might have dual differentiations.
More importantly, the interpretation of TCR--GR itself
should be modified now as a corollary to our analysis of the KIR
repertoire in sinonasal lymphoma. A polyclonal TCR-GR is no
longer equivalent to a reactive T-cell proliferation, because there is
still the possibility of a monoclonal process due to NK-cell
proliferation. Furthermore, a monoclonal TCR-GR is no longer
equivalent to a T-cell lymphoma, because the possibility of a lymphoma
with dual T/NK differentiation cannot be excluded. We suggest that an
isolated analysis for either the TCR or KIR repertoire is no
longer sufficient, but that they could be done together for more
accurate lineage assignment than either one alone.
In summary, we present a novel approach to the lineage assignment of
sinonasal lymphoma, based on the consideration of a restricted KIR
repertoire as a criterion of monoclonal or oligoclonal NK-cell
proliferation. Our data showed that most sinonasal lymphomas have a
restricted KIR repertoire. This is consistent with and provides
preliminary support for the hypothesis. We conclude that a restricted
killer cell immunoglobulin-like receptor repertoire without
TCR--GR can be used to support a true NK-cell lineage in
a subset of sinonasal lymphomas.
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Acknowledgements |
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Footnotes |
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Supported, in part, by grants 89-N027, 89-B-FA01-1-4, NSC892320-B-002-276, NHRI-EX90-8704SL, and NHRI-GT-EX89S704L from National Taiwan University Hospital, National Science Council, and National Health Research Institute, Taiwan.
Accepted for publication July 17, 2001.
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References |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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proteins in activated human adult NK cells and CD3,
, complexes in fetal NK cells: implications for the relationship of NK and T lymphocytes. J Immunol 1992, 14:1876-1880
, proteins. J Exp Med 1982, 175:1055-1066 gene rearrangement in paraffin-embedded tissue by polymerase chain reaction and nonradioactive single-strand conformational polymorphism analysis. Am J Pathol 1999, 154:67-75This article has been cited by other articles:
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