Molecular Genetics of Head and Neck Cancer

Lyon L. Gleich, MD, Frank N. Salamone, MD

Cancer Control. 2002;9(5)

Molecular Determination of Surgical Margins

An analysis of the histologically negative margins from 25 head and neck cancer patients demonstrated p53 mutations in 13 of these patients. None of the patients with histologically and genetically negative margins recurred, while 5 of the 13 patients with p53 mutation in the margin recurred locally.^[95] In another study, surgical margins from patients who underwent larynx cancer resections were tested for eIF4E status.^[96] Of the 54 patients studied, 32 had eIF4E-positive margins. Of the 25 patients who recurred, 21 had eIF4E-positive margins. These studies show that histologically negative margins are not necessarily genetically negative and that genetically positive margins are more likely to recur. However, the relevance of this information in clinical management has not yet been fully elucidated.

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Cite this: Molecular Genetics of Head and Neck Cancer - Medscape - Sep 01, 2002.

Abstract and Introduction
Tumor Suppressor Genes
Oncogenes
Multiple Molecular Aberrations in Head and Neck Cancers
Molecular Immunology
Molecular Detection of Head and Neck Cancers
Molecular Determination of Surgical Margins
Gene Therapy
Biologic Therapy
Conclusions
References

Table 1. Selected Studies of p53 Expression and Mutation That Included Evaluation of Prognosis
Study, Year	Patients	Method	p53 Abnormal	Measure	Results
Bova et al 1999^[3]	143	IHC	62%	Survival	No correlation
Bradford et al 1995^[4]	178	IHC	61%	Organ preservation	More likely with staining
Hirvikoski et al 1997^[5]	103	IHC	68%	Survival	Better with staining
Kapranos et al 2001^[6]	93	IHC	48%	Survival	No correlation
Kaur et al 1998^[7]	145	IHC	70%	Survival	Worse with staining only for oral cavity cancer
Kokoska et al 1996^[8]	66	IHC	61%	Survival	No correlation
Mao et al 1995^[9]	111	IHC	69%	Survival	No correlation
Michalides et al 1997^[10]	115	IHC	42%	Survival	No correlation
Narayana et al 2000^[11]	102	IHC	37%	Survival	No correlation
Osaki et al 2000^[12]	225	IHC	57%	Survival	Worse with staining
Portugal et al 1997^[13]	100	IHC	66%	Survival	No correlation
Pruneri et al 1998^[14]	149	IHC	50%	Survival	No correlation
Raybaud-Diogene et al 1997^[15]	101	IHC	49%	Recurrence	Worse with staining
Wilson et al 1995^[16]	99	IHC	76%	Survival	No correlation
Gleich et al 1996^[17]	50	LOH	38%	Survival	No correlation
Bradford et al 1997^[18]	44	PCR	39%	Survival	Worse with mutation
Chomchai et al 1999^[19]	45	PCR	33%	Survival	Better with mutation
Hegde et al 1998^[20]	39	PCR	33%	Survival	Worse with mutation
Hiranuma et al 1998^[21]	45	PCR	40%	Survival	No correlation
Hogmo et al 1999^[22]	34	PCR	59%	Recurrence	No correlation
Koch et al 1996^[23]	110	PCR	44%	Survival	No correlation
Ostwald et al 2000^[24]	94	PCR	43%	Survival	No correlation
Saunders et al 1999^[25]	42	PCR	48%	Recurrence	No correlation
Shima et al 2000^[26]	46	PCR	43%	Survival	No correlation

Table 2. Selected Studies of Retinoblastoma (Rb) Expression and Mutation
Study, Year	Patients	Method	Rb Abnormal	Measure	Results
Dokiya et al 1998^[28]	72	IHC	29%	Survival	Worse with abnormality
El-Naggar et al 1999^[29]	35	IHC	6%
Ioachim et al 1999^[30]	41	IHC	30%
Koontongkaew et al 2000^[31]	53	IHC	74%
Nakahara et al 2000^[32]	78	IHC	56%
Pande et al 1998^[33]	35	IHC	66%
Pavelic et al 1996^[34]	182	IHC	27%	Survival	T1 tumors worse with abnormality
Regezi et al 1999^[35]	55	IHC	40%
Xu et al 1998^[36]	34	IHC	9%
Gleich et al 1996^[17]	57	LOH	37%	Survival	No correlation
Scholnick et al 1994^[37]	37	LOH	59%
Yokoyama et al 1996^[38]	28	LOH	14%
Sartor et al 1999^[39]	25	Western blot	44%

Table 3. Studies of p16 Expression and Mutation
Study, Year	Patients	Method	p16 Abnormal	Measure	Results
Bova et al 1999^[3]	143	IHC	55%	Survival	Worse with abnormality
El-Naggar et al 1999^[24]	35	IHC	89%
Pande et al 1998^[33]	35	IHC	63%
Jares et al 1997^[43]	42	LOH	57%	Nodal metastasis	More with abnormality
Danahey et al 1999^[44]	26	PCR	58%	Recurrence	More with abnormality
Jares et al 1999^[43]	46	PCR	22%
Matsuda et al 1996^[45]	20	PCR	20%
Olshan et al 1997^[46]	33	PCR	36%
Sartor et al 1999^[39]	26	PCR	19%
Shintani et al 2001^[47]	32	PCR	56%
Sartor et al 1999^[39]	26	Western blot	69%

Table 4. Studies of p21 Expression
Study, Year	Patients	Method	p21 Expression	Measure	Results
Agarwal et al 1998^[50]	51	IHC	69%
Erber et al 1997^[51]	42	IHC	67%	Survival	Worse with staining
Hirvikoski et al 1999^[52]	144	IHC	68%	Survival	No correlation
Jeannon et al 2000^[53]	60	IHC	58%	Survival	Worse with staining
Kapranos et al 2001^[6]	93	IHC	55%	Survival	No correlation
Kuo et al 1995^[54]	51	IHC	92%	Nodal metastasis	More with staining
Mineta et al 1999^[55]	72	IHC	29%	Survival	No correlation
Ng et al 1999^[56]	88	IHC	82%
Osaki et al 2000^[12]	225	IHC	29%	Survival	No correlation
Pruneri et al 1999^[57]	132	IHC	69%	Metastasis	Less with staining
Ralhan et al 2000^[58]	30	IHC	53%
Regezi et al 1999^[35]	64	IHC	77%
Saunders et al 1999^[25]	36	IHC	86%
Tatemoto et al 1998^[59]	150	IHC	29%	Nodal metastasis	More with staining
van Oijen et al 1998^[60]	43	IHC	67%
Yook et al 1998^[61]	20	IHC	75%	Survival	No correlation
Yuen et al 2001^[62]	87	IHC	56%	Survival	Better with staining

Table 5. Studies of p27 Expression
Study, Year	Patients	Method	p27 Expression	Measure	Results
Kapranos et al 2001^[6]	93	IHC	53%	Survival	No correlation
Kudo et al 2000^[63]	17	IHC	18%
Mineta et al 1999^[55]	81	IHC	32%	Survival	Better with staining
Pruneri et al 1999^[57]	132	IHC	62%	Survival	Better with staining
Tamura et al 2001^[64]	102	IHC	47%	Survival	Better with staining

Table 6. Studies of Cyclin D1 Expression and Amplification
Study, Year	Patients	Method	Cyclin D1 Abnormal	Measure	Results
Okami et al 1999^[66]	11	FISH	36%
Akervall et al 1997^[67]	75	IHC	12%	Survival	Worse with staining
Bova et al 1999^[3]	147	IHC	68%	Survival	Worse with staining
Capaccio et al 1997^[68]	96	IHC	44%	Nodal metastasis	More with staining
Koontongkaew et al 2000^[31]	53	IHC	40%
Kyomoto et al 1997^[69]	45	IHC	53%	Survival	Worse with staining
Masuda et al 1996^[70]	42	IHC	55%	Survival	Worse with staining
Michalides et al 1997^[10]	115	IHC	49%	Survival	Worse with heavy staining
Mineta et al 2000^[55]	94	IHC	19%	Survival	Worse with staining
Nakahara et al 2000^[32]	78	IHC	36%
Pignataro et al 1998^[71]	149	IHC	32%	Survival	Worse with staining
Bellacosa et al 1996^[72]	51	Southern blot	18%	Survival	Worse with amplification
Callender et al 1994^[73]	32	Southern blot	34%
Fortin et al 1997^[74]	50	Southern blot	20%	Survival	No correlation
Gleich et al 1999^[75]	24	Southern blot	42%	Survival	No correlation
Meredith et al 1995^[76]	56	Southern blot	39%	Survival	Worse with amplification
Muller et al 1997^[77]	201	Southern blot	58%	Survival	No correlation

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