• oncogene;
  • chromosomal abnormality;
  • squamous cell carcinoma;
  • head and neck;
  • prognosis


  1. Top of page
  2. Abstract
  6. Acknowledgements


Abnormalities of chromosome band 11q13 are frequent in squamous cell carcinoma of the head and neck (SCCHN). The oncogene CCND1 is located at 11q13 and encodes cyclin D1, a cell cycle-regulating protein. The authors investigated the clinical relevance and associations between amplification and overexpression of cyclin D1 and 11q13 rearrangements.


The study involved two series of patients. In Series 1, overexpression of cyclin D1 and 11q13 rearrangements, assessed by immunohistochemistry and cytogenetics, respectively, were compared with clinical data in 75 patients with SCCHN. Patients were monitored for at least 18 months or until death. In another 23 patients (Series 2), the authors investigated the association between DNA amplification (by slot blot hybridization), overexpression of cyclin D1, and cytogenetics.


In Series 1, 9 of 75 tumors (12%) had 11q13 aberrations, 6 of which manifested elevated expression of cyclin D1. Patients with tumors strongly positive for cyclin D1 (n = 9) and those with tumors showing 11q13 rearrangements had poorer survival (P = 0.047 and 0.005, respectively). However, the correlation between these two variables was weak (P = 0.12). In Series 2, 17 of 23 tumors (74%) showed elevated cyclin D1 protein expression, and 6 of these showed gene amplification as well. Of these six, only one revealed 11q13 rearrangements.


Overexpression of cyclin D1 and 11q13 rearrangements are independent prognostic factors for SCCHN. In general, DNA amplification results in overexpression of cyclin D1, but additional genetic mechanisms are involved in the deregulation. Furthermore, oncogenes at 11q13 besides CCND1 may be involved in the tumorigenesis. Cancer 1997; 79:380-9. © 1997 American Cancer Society.

The TNM classification system does not fully predict clinical outcome in cases of squamous cell carcinoma of the head and neck (SCCHN).1 In order to optimize treatment of patients, attempts are being made to establish new prognostic indicators, among which we have studied chromosomal abnormalities and deregulated oncogenes.

The CCND1 gene (PRAD-1) is a putative oncogene reported to be overexpressed in many types of human cancer. It encodes the cell cycle regulating cyclin D1 protein involved in the G1 to S transition. Three members of the human cyclin D gene family have been identified. CCND1 is located at chromosome band 11q13,2-4 and CCND2 and CCND3 are located at chromosome bands 12p13 and 6p21, respectively.5-7 The three human D-type genes share an average of 57% identity over the entire coding region, but each member of the gene family may play a distinct role in cell cycle progression.6

CCND1 can be deregulated by inversion,8, 9 translocation,10 and amplification. Amplification of CCND1 has an impact on the expression of cyclin D1, causing potential for growth advantage and enhancing tumorigenesis.3, 4 The gene is amplified and overexpressed in some esophageal carcinomas,11, 12 breast carcinomas,13 and SCCHN.14 Amplification of CCND1 in SCCHN is correlated with aggressive tumor growth15-18 and poor prognosis.19 Recently, overexpression of cyclin D1, detected by immunohistochemistry (IHC) in archival specimens, was reported to be associated with recurrence and shortened overall survival in operable cases of SCCHN.20

Cytogenetic analysis of short term cultured tumor specimens has revealed a large variety of chromosomal abnormalities in SCCHN.21 Chromosome band 11q13 is frequently rearranged,21-23 often as a homogeneously staining region (hsr), i.e., a cytogenetic sign of amplification. Aberrations at 11q13 have recently been reported to correlate with poor prognosis.24

Thus, several reports indicate that deregulation of CCND1, i.e., at the chromosome, gene, and protein levels, is important in SCCHN development. So far, however, no attempts have been made to investigate whether there is a direct relation between cytogenetic, molecular genetic, and immunohistochemical evidence of such deregulation. The aim of the current study was to assess amplification and overexpression of CCND1/cyclin D1 in cytogenetically characterized cases of SCCHN. We compared the results with clinical outcome in order to investigate the prognostic value of these variables.


  1. Top of page
  2. Abstract
  6. Acknowledgements

Patients and Tumors

Tumor samples were obtained from diagnostic biopsies or at surgery, consecutively collected during the period 1987 through 1994. However, fresh frozen tissue for slot blot hybridization (SBH) was only available from 1990; and so, in order to present our findings in a comprehensive manner, we report them in two series. All tumors were reclassified according to UICC criteria.25

Series 1 included 75 patients (60 men and 15 women). Mean age at diagnosis was 63.5 years (range, 22-98.3 years). Tumor samples were obtained from patients with primary, untreated SCCHN during the period 1987 through 1991. All patients received standardized therapy with any, or a combination, of the following modalities: surgery, radiotherapy, or chemotherapy.24 The cytogenetic findings have been reported as part of a larger material (n = 116) in a study of cytogenetics and prognosis in SCCHN.24 In many of these cases there was not enough tissue to prepare specimens for IHC, and as a result only 75 patients could be included in the present investigation. TNM classification of the tumors and the patients' clinical courses are given in Table 1. Thirty-six patients (48%) were T1 or T2, and 39 patients (52%) were T3 or 4. Twenty-eight patients (37%) showed lymph node metastases at diagnosis. Six different subsites were represented: oral cavity in 28 patients, oropharynx in 20, nasopharynx in 1, hypopharynx in 6, maxillary sinus in 2, and larynx in 18. The patients were followed for at least 18 months or until death.

Table 1. TNM Classification, Cytogenetic Analysis, Cyclin D1 Expression, and Clinical Courses in 75 Patients with Squamous Cell Carcinoma of the Head and Neck (Series 1)
Patient no.SiteTNMKaryotype11q13 aberrationCyclin D1 expressionStatusSurvival (mos)
  1. +: positive; +/-: weakly positive; ++: strongly positive; -: negative; Trig: trigonum; N: normal karyotype; Num: numerical changes only; S: simple structural aberrations (<3); Cx: complex karyotype (>3 structural aberrations); hsr: homogeneously staining region; add: additional chromosomal material; dmin: double minute chromosome; DOD: dead of disease; NED: no evidence of disease; DID: dead of intercurrent disease.

2Oropharynx300N-+/-Alive NED70
4Larynx200S--Alive NED65
6Larynx100S--Alive NED62
7Larynx200S--Alive NED56
8Oropharynx200N--Alive NED62
9Floor of mouth301CxTransloc-DOD21
10Larynx200Cx-+Alive NED57
12Trig. retromolare410Num-+DOD7.5
14Larynx300Num--Alive NED49
15Larynx200Num--Alive NED1.5
16Trig. retromolare200S-++Alive NED45
17Floor of mouth300S-++Alive NED54
20Epipharynx200N--Alive NED52
21Larynx300S--Alive NED40
25Maxill200Num-+Alive NED47
27Trig. retromolare400Num-+/-Alive NED38
29Floor of mouth320Num--DOD17
33Trig. retromolare110N--DOD5
35Larynx200S-+/-Alive NED41
37Lip200N-+Alive NED44
40Floor of mouth200Num--Alive NED37
41Tongue200S--Alive NED39
42Oropharynx410Cx, dminAdd-DOD5.5
45Oropharynx220N--Alive NED37
47Oropharynx220N--Alive NED36
49Maxill400N--Alive NED33
52Floor of mouth410CxHsr-DOD14
53Floor of mouth130N--DOD7
55Trig. retromolare310Cx, hsr--DOD9
56Larynx200S-+/-Alive NED28
58Oropharynx300N-+Alive NED29
59Oropharynx320Cx--Alive NED29
60Floor of mouth210Cx--DOD21
62Tongue200Num--Alive NED27
63Trig. retromolare100N--DOD20
66Floor of mouth420Cx-+Alive NED25
67Larynx200Cx--Alive NED24
68Oropharynx420Cx-+/-Alive NED23
70Gingiva110Num--Alive NED22
72Hypopharynx220N-+Alive NED21
73Larynx300Num--Alive NED16
74Gingiva200Cx--Alive NED17

Series 2 comprised 23 patients with SCCHN, from whom samples were collected between 1990 and 1994. All samples were stored at -80 °C in dimethylsulfoxide-citrate buffer until analysis. They were derived from the oral cavity in 9 patients, the hypopharynx in 4, the oropharynx in 3, the larynx in 4, and the esophagus in 2. One tumor sample was collected from a lymph node metastasis from a carcinoma of the lip. Three of the patients who contributed specimens had other prior or synchronous malignancies.


The methods used for cell culture and chromosome preparations have previously been described in detail.21, 26 Tumor samples from the period 1987 through 1989 (n = 52) were cultured in a medium containing serum,26 whereas samples from 1990 onward (n = 24) were cultured in a chemically defined, serum-free medium.21 The clonality criteria and the descriptions of karyotypes were in accordance with the International System for Human Cytogenetic Nomenclature (1991).27

The tumors were divided into four subgroups, according to the cytogenetic findings: normal karyotype, numerical changes only, simple structural rearrangements (not more than three in any clone), and complex karyotype (at least four different structural rearrangements in one clone).


The procedure of producing antibodies against cyclin D1 and IHC staining have been described in detail previously.20 To describe the procedure briefly: An antiserum against cyclin D1 was generated by injection of a beta-galactosidase-cyclin D1 fusion protein into rabbits. For IHC staining of the paraffin-embedded archival specimens, an affinity-purified polyclonal antibody, B31S, was used. All IHC results were assessed by two observers (B.L. and M.D.) who were unaware of the cytogenetic findings, tumor site, TNM status, stage of disease, and the patients' clinical courses. IHC results were scored as follows: negative (-); 0-5% of the tumor cells positive (+/-); 5-50% positive (+); and >50% positive (++).

Slot Blot Hybridization

Genomic DNA (5 μg) was denatured with alkali and applied to a nylon membrane with a slot blotting device (BioRad Laboratories, Richmond, CA). The membrane was neutralized, air-dried, and hybridized to a random primer radiolabeled cDNA probe for the CCND1 gene (clone pHsCYCD1-H123, kindly provided by Dr. David Beach, CSH Laboratories, Cold Spring Harbor, NY). Denatured probe (106 counts per minute [cpm] DNA/mL hybridization solution) was hybridized to single-stranded prehybridized membrane-bound DNA at 65 °C in hybridization solution overnight with constant shaking. The membrane was washed under stringent conditions and exposed to X-ray film at -70 °C overnight or longer. The membrane was rehybridized with a control probe for the progesterone receptor (PGR) gene (clone HPR-54, kindly provided by Dr. Bert W. O'Malley, Baylor College of Medicine, Houston, TX), serving as a negative control, localized at 11q22-q23, after removal of the bound probe from the membrane at the denaturing temperature.

The analyses were performed by two observers (Å.B. and H.M.) who were unaware of the cytogenetic and immunohistochemical findings. The amplification findings were divided into three groups: weak (+), moderate (++), and strong (+++). The approximate number of gene copies for these groups were as follows: +: 2-5 copies, ++: 6-10, and +++: >10 (data not shown).

To detect any crossreactivity between the CCND1 cDNA probe and CCND2 and CCND3, control experiments were performed with slot blotted DNA hybridized to a DNA probe for the INT2 gene (the INT2 cDNA clone SS6, kindly provided by Dr. Clive Dickson, ICRF Laboratories, London, UK), which is located close to CCND1 on 11q13 and usually coamplified with CCND1 in some tumor types.

The specificity and stringent conditions in hybridization of all three probes (for CCND1, INT2, and PGR genes) have previously been tested in separate Southern blot analyses (data not shown).

Statistical Analysis

Statistical analysis of the data was performed with True Epistat software (Epistat Services, Richardson, TX). The chi-square test and Fisher's exact test were used to investigate differences among groups showing different IHC and cytogenetic findings. Survival curves were plotted by the Kaplan-Meier method, and differences in survival were calculated with the log rank test. Cox proportional hazards model was used for multivariate analysis to determine whether the parameters were confounded by other variables.


  1. Top of page
  2. Abstract
  6. Acknowledgements

Series 1

Cytogenetics and immunohistochemistry

Thirty-one of 75 tumors (41%) expressed cyclin D1 by IHC, 9 (12%) of which were strongly positive (++) (Table 1). In all 31 cases, only the nuclei were stained. Three cases showed cytoplasmic staining of cyclin D1 and were considered negative in the analysis. Nine of 75 tumors (12%) showed 11q13 rearrangements (hsr in 4 cases, addition of unknown chromosomal material in 3, and translocations in 2). Six of these 9 tumors expressed cyclin D1 at different levels, 3 of which were cyclin D1 ++ (Table 2 and Fig. 1). Nineteen of 75 tumors (25%) had a complex karyotype, and within this cytogenetic subgroup 9 (47%) expressed cyclin D1.

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Figure 1. Patient 36 from Series 1 is represented (see Tables 1 and 2). (A) A complex karyotype with a homogeneously staining region at 11q13 in cytogenetic analysis is shown (breakpoints are marked by arrows). (B) Cyclin D1 is shown to be strongly positive (++) by immunohistochemistry.

Table 2. Expression of Cyclin D1 in 9 Patients with 11q13 Rearrangements (Series 1)
Patient no.KaryotypeaCyclin D1 expression
  • +: positive; +/-: weakly positive; ++: strongly positive; -: negative.

  • a

    Karyotypes have been reported previously.21,26,39

  • 11q13 aberrations are given in bold type. For further clinical information, see Table 1.

166-76,XX,-Y,+1,+3,-4,del(4)(q31), +i(5)(p10)×2, -6, del (7)(q31),del(8)(p21),+add(10)(q26),add(11)(q13),-13,-13,-13,+del(16)(q22), -18,+20,+20,+2-6mar+
346,XX,+der(1)t(1;12)(p11;P11)ins(1;11)(q32;q13q22)del(11)(q13q22),-12,der(17)t(1;17)(q42;p13)/+ 11 other unrelated, pseudodiploid clones.+/-
945,X,+X,-Y,add(3)(p11),add(5)(q35),+der(11)t(11;13)(q13;q12),-13,add(13)(p13),-14,i(15)(q10),der(21)t(9;21)(q13;p13),der(21)t(18;21) (q11;p13)-
2838-41,X,-Y,der(1)t(1;10)(p12;q11),add(2)(p11-13),i(3)(q10),der(4)t(4;13)(p12;q11),i(8)(q10),-9,-10,-10,der(11)t(1;11)(p12;q13)hsr(11) (q13),-13,-13,add(14)(q32),der(15;21)(q10;q10),der(16)t(9;16)(q13;p13),inv(18)(p11q22),+2-3mar++
3665-73,X,add(X)(p11),der(X)t(X;14)(q22;q24),t(1;5)(p21;q21), del(3)(p23p25),add(4)(q34),-6,i(8)(q10),-9,add(11)(p11),der(11)add(11) (q13)hsr(11)(q13),der(11)t(9;11)(q13;q13)hsr(11)(q13),-12,-13,der(13;22)(q10;q10),-14,add(14)(q32),-15,add(15)(p?),add(17)(p13), dic(18;?),(q23;?),-19,+20,+20,-21,+1-5mar++
4259-60,-X,-X,-Y,-1,-2,del(2)(q13),der(2)t(2;8)(q33;q13),der(3)t(3;4)(p25;q11),i(4)(q10),der(4)t(4;12)(q11;q15),-5,del(7)(q11),+add(7) (q11),-8,der(8)t(8;8)(p11;q13),-9,add(11)(q13),i(12)(p10),der(12)(p11q13),+der(12)t(3;12)(q11;q24),-13,der(13)t(5;13)(p11;q13), der(13)t(3;13)(p11;q14),-14,der(15)t(15;17)(p11;q11),+der(15;21)(q10;q10),-17,der(17)t(7;17;?)(q11;p13;?),-18,-18,-18, add(19)(p13),+20,-21,-21,-21,-22,der(22)t(11;22)(p11;p11),dmin,+2-7mar-
5238-40,X,-Y,-3,-4,-5,der(5)t(1;5)(p22;p14),+add(6)(q15),i(7)(q10),der(7)t(4;7)(q11;q22),-8,-9,der(11)t(4;11)(q21;p15),inv(11)(p13q25), +der(11)add(11)(q13)hsr(11)(q13),-12,-14,i(14)(q10),der(15)t(3;15)(p11;p11)inv(3)(p13p21),add(16)(p13),-17,-18,-22,+2-4mar-
6569-72,XX,-Y,der(2)add(2)(p11)hsr(2)(p11),+3,-4,-5,i(5)(q10),-8,-9,-9,-10,-10,hsr(11)(q13),-12,i(12)(q10),-13,-13,i(14)(q10), +add(15)(p11),+16,+20,+20,+add(22)(p11),+7-10mar+/-
7172-79,XX,-Y,+add(1)(p11),+2,+3,i(3)(q10)×2,+4,der(4)t(4;7)(p15;p13)×2,+5,+6,add(6)(p23)×2,+7,i(8)(q10),+der(8)t(8;?9) (p11;q13),-9,-9,-9,+11,der(11)trp(11)(q14q22)add(11)(q23)×2 or add(11)(q13)×2,-13,-13,+14,der(14;17)(q10;q10)×2, der(15;22)(q10;q10)×3,+der(15;22),-16,-17,+18,dup(18)(q22q23)×2,+19,add(19)(p13)×2,+20,-21,-21,-21,+3-5mar++

Survival, with respect to death from SCCHN, was shorter for patients with cyclin D1 ++ tumors than for all other patients (P = 0.047) (Fig. 2). No other level of overexpression was associated with poor clinical outcome when compared with patients with tumors not expressing the protein. Patients with 11q13 rearrangements fared worse than patients without these changes (P = 0.005) (Fig. 3). In addition, there were no differences in the distribution of T or N classification, stage, or age between the cyclin D1 ++ subgroup and the subgroup with any other IHC findings or between the 11q13 subgroup and the non-11q13 subgroup. A multivariate analysis was performed for the following four factors: cyclin D1 overexpression, 11q13 rearrangements, T classification, and N classification. All four turned out to be independent prognostic factors. The relative risk was calculated to approximately 3 for all of them (Table 3).

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Figure 2. Survival analysis with respect to death from squamous cell carcinoma of the head and neck (n = 75) is shown. Patients with tumors strongly cyclin D1 positive (++) versus patients with all other expressions of cyclin D1 (-: negative; +/-: weakly positive; +: positive) are represented; P = 0.047 (log rank test).

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Figure 3. Survival analysis is shown with respect to death from squamous cell carcinoma of the head and neck (n = 75). Patients with versus without 11q13 rearrangements are represented; P = 0.005 (log rank test).

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Table 3. Multivariate Analysis (Cox Proportional Hazards Model) of Overexpression of Cyclin D1, 11q13 Rearrangements, and T and N Status in 75 Patients with Squamous Cell Carcinoma of the Head and Neck
VariableRelative risk95% confidence interval
  1. N+: lymph node metastases present; ++: strongly positive.

Overexpression of cyclin D1 (++ vs. any other expression)31.2-7.4
11q13 rearrangements (present vs. not present)2.61.2-6.1
T status (T3-4 vs. T1-2)3.11.4-6.8
N status (N + vs. N0)3.61.7-7.6

There was no significant covariation of 11q13 rearrangements and cyclin D1++ in the total material (P = 0.12) or in the cytogenetic subgroup of tumors with complex karyotype (P = 0.09). The distribution of 12 other chromosome aberrations repeatedly detected in SCCHN, i.e., loss of material from 3p, 4p, 5p, 5q, 8p, 9p, 11q, 13q, and 14q and gain of material from 7q, 8q, and 15q, did not vary with overexpression of cyclin D1 (data not shown).

Series 2

Slot blot hybridization, immunohistochemistry, and cytogenetics

Table 4 shows the SBH, IHC, and cytogenetic findings. Seven of 23 tumors (30%) were cyclin D1 positive (+) and another 10 weakly positive (+/-) by IHC. The CCND1 gene was amplified in 6 of 23 tumors (26%) at various levels. There was only a statistical trend of correlation between the two parameters (P = 0.15). However, all 6 tumors with CCND1 amplification expressed cyclin D1.

Table 4. Amplification and Expression of CCND1/Cyclin D1 and 11q13 Rearrangements in 23 Patients with Squamous Cell Carcinoma of the Head and Neck (Series 2)
Patient no.SiteCCND1 ampl.Cyclin D1 expr.11q13 rearr.
  • ampl: amplification; expr: expression; rearr: rearrangements; met: metastases; +: positive; +/-: weakly positive; ++: moderately positive; +++: strongly positive; -: negative; n.d.: not determined; Hsr: homogeneously staining region; Dic: dicentric chromosome.

  • a

    11q13 rearrangements in recurrent tumor two years later.

8Floor of mouth-+/--
9Floor of mouth+++/--
11Floor of mouth-+-
12Floor of mouth-+/--
15Floor of mouth-+/--
22Floor of mouth-+/-Failure
23Lip (lymph node met.)---

The two different probes used (INT2 cDNA clone SS6 and pHsCYCD1-H123) detected amplification of the 11q13 region in the same tumors at equal levels (data not shown). Although it cannot be ruled out that some degree of crossreactivity between the CCND1 cDNA probe and the cyclin D2 and D3 genes is present, these findings argue against such an interference. The control experiments with the INT2 probe were performed in 15 of 23 tumors (65%) (Patients 1-15, Table 4).

Cytogenetic analysis revealed two patients with tumors showing 11q13 rearrangements (Table 4), one of whom was represented by an hsr (Patient 7). This case was strongly amplified but showed weak staining in IHC (+/-) (Fig. 4). The second patient (Patient 13) had a dic(11;20)(q13;q13) with no corresponding amplification or expression of cyclin D1. Patient 21 had a pseudodiploid karyotype, which might not be representative of the tumor, with no 11q13 rearrangements. This tumor was moderately amplified and cyclin D1+. Two years later, the patient had recurrent disease and the new tumor had a complex karyotype with an 11q13 translocation (data not shown). The cohort in Series 2 (n = 23) was considered too small, and the follow-up too short, to perform survival analysis.

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Figure 4. Patient 7 from Series 2 is represented (see Table 4). (A) A homogeneously staining region at 11q13 is shown. (B) Strong amplification is represented (Patient 8, with no amplification, and, to the right, results from the negative control gene, PGR). (C) Weak expression of cyclin D1 (+/-) is represented.


  1. Top of page
  2. Abstract
  6. Acknowledgements

In Series 1 we observed a deregulated cyclin D1 expression, ranging from +/- to ++, in 31 out of 75 tumors (41%) (Table 1). Nine tumors (12%) showed 11q13 rearrangements. These results are in accordance with earlier IHC and cytogenetic findings.20, 21, 28 In molecular genetic studies, amplification of 11q13 has been reported in 25-38% of patients,17, 18, 29, 30-33 as compared with 26% in the current study. The lower frequency of 11q13 rearrangements detected by cytogenetics rather than by molecular genetic techniques might in part be due to difficulties in obtaining tumor representative metaphase spreads of good quality. Another explanation might be submicroscopic amplifications, which are not detectable at the chromosome level.

This study addressed the clinical relevance and the association among three different parameters, amplification and overexpression of CCND1/cyclin D1 (measured by SBH and IHC, respectively) and 11q13 rearrangements (cytogenetically analyzed). Each of these parameters is associated with a poor prognosis,19, 20, 24 but do they reflect the same genetic mechanism?

In Series 1, 3 of 9 cases showing 11q13 rearrangements were cyclin D1 negative. In Series 2, the corresponding rate was one of two. Despite the small numbers, the presence of 11q13 aberrations without cyclin D1 overexpression and the significant association between 11q13 rearrangements and prognosis strongly suggest that other putative oncogenes within the amplicon besides cyclin D1 may be involved in the tumorigenesis. The role of these other putative oncogenes, e.g., EMS-134, 35 or tumor suppressor genes, remains to be elucidated. In breast carcinoma, amplification of 4 independent markers at 11q13, including CCND1, have been reported.36

It cannot be ruled out that some chromosome aberrations involving 11q13 represent mutations with little or no phenotypic impact that arise as a result of increased genetic instability in the tumor cells. However, an earlier study has indicated that these findings represent genetic events more specifically involved in the tumorigenesis of SCCHN, as 11q13 rearrangements defined a subgroup of tumors with complex karyotype that correlated with worse prognosis than those with tumors showing complex karyotype only.24

We observed that the level of cyclin D1 expression in Series 2 increased along with an increasing degree of amplification (as assessed by SBH), although the number of patients was considered too small to allow any statistical evaluation. These findings suggest that amplification generally results in overexpression, and this agrees with earlier findings.37, 38 However, 11 tumors manifested increased expression without any amplification, and there was a weak overall correlation between the 2 parameters. Thus, other genetic mechanisms besides amplification must be involved in the deregulation of CCND1, such as translocations, inversions, or yet unknown causes of transcriptional activation. Activation by inversion has been demonstrated in parathyroid adenomas8, 9 and by translocations in B-cell leukemias and lymphomas.10 Frequent translocations involving 11q13 have been described in SCCHN.39 Furthermore, growth factor stimulation results in elevated expression of cyclin D1.40 Because EGF-R is amplified and overexpressed in SCCHN,41, 42 overexpression of growth factors might be another mechanism in the deregulation of cyclin D1.

In the current study, patients with tumors strongly positive (++) for cyclin D1 by IHC had a poor prognosis. These findings are in accordance with earlier reported data20 and support the hypothesis that deregulation of CCND1 is a sign of biologic aggressiveness in SCCHN. Chromosomal abnormalities involving 11q13 also correlated with poor clinical outcome, as described in a previous study.24 Thus, we conclude that the two parameters, as studied by IHC and cytogenetics, are reliable and clinically useful predictors of outcome in SCCHN, independent of such established prognostic factors as T and N classification.


  1. Top of page
  2. Abstract
  6. Acknowledgements

The authors thank Ms. Petra Kristel for excellent technical assistance and Harald Andersson, Ph.D., for valuable statistical advice.


  1. Top of page
  2. Abstract
  6. Acknowledgements
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