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Research Letter |

Correlation of Subjective Self-reported Melanoma Growth Rate With Objective Tumor Proliferation Markers FREE

Wenyuan Liu, MBChB, MD; Grant A. McArthur, MBBS, PhD; Melanie Trivett, PhD; William K. Murray, MBBS; Rory Wolfe, BSc, PhD; John W. Kelly, MBBS, MD
Arch Dermatol. 2008;144(4):555-556. doi:10.1001/archderm.144.4.555.
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Previous studies, using patient recall, have suggested that melanoma growth rate may be an independent prognostic marker1 and that rapid growth tends to occur in older men and have nodular morphologic characteristics and a different clinical presentation from other melanomas.2

Retrospective recall of time delay leading up to melanoma diagnosis is regarded by some as unreliable.3 However, there is no other practical method by which to evaluate the evolution of a melanoma from the outset. In a previous study,2 the ratio between Breslow thickness and time interval for a melanoma to develop was used as an estimate for melanoma rate of growth (ROG). This subjective measure of ROG based on patient recall correlated significantly with mitotic rate, an objective measure of melanoma proliferation, indicating the validity of patient recall to provide a surrogate measure of melanoma growth rate.2

To further evaluate the relationship between ROG and melanoma proliferation, we assessed the correlation of ROG with Ki67, a commonly used marker of cell cycle progression,4 and phosphorylated-histone-H3 (PH3), a sensitive marker of mitosis.5 The methods of assessing Ki67 and PH3 have been described elsewhere.6 In brief, recuts of a representative section within the primary melanoma were used for immunohistochemical staining with both markers, and staining was scored by 2 independent assessors without knowledge of ROG. The Ki67 staining (percentage of staining melanoma cells in the dermis) and the PH3 staining (numbers of staining melanoma cells per millimeters squared in the dermis) were assessed, beginning in the most immunoreactive area. The final score of Ki67 and the final score of PH3 were defined as the mean of scores from the 2 assessors.

The intraclass correlation coefficients for interassessor agreement were 0.91 for PH3 and 0.89 for Ki67, indicating an excellent level of agreement.6 We found that similar to the correlation with mitotic rate, ROG was significantly associated with the Ki67 score (Spearman rank correlation coefficient, 0.44; P < .001) (Figure 1) and with the PH3 score (Spearman rank correlation coefficient, 0.46; P < .001) (Figure 2).

Place holder to copy figure label and caption
Figure 1.

Scatterplot of the relationship between the Ki67 score and the clinical rate of growth.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

Scatterplot of the relationship between phosphorylated-histone H3 (PH3) score and the clinical rate of growth.

Graphic Jump Location

Although retrospective recall of events leading up to a diagnosis of melanoma is associated with several potential sources of error,2 clinical history remains the only practical tool to assess the evolution of melanomas from their inception. Herein, we have demonstrated a significant correlation between the patient-recall–based ROG and objective assessments of melanoma proliferation using immunohistochemical markers at the time of excision. One limitation of this comparison is that ROG examines the development of a melanoma over its whole course, whereas immunohistochemical markers examine only the state of proliferation at the time of removal.

These findings provide further evidence for the value of ROG in the clinical assessment of melanoma growth kinetics.

ARTICLE INFORMATION

Correspondence: Dr Liu, Victorian Melanoma Service, Alfred Hospital, PO Box 315, Prahran, Melbourne, Victoria 3181, Australia (wenyuan_liu@hotmail.com).

Financial Disclosure: None reported.

Grob  JJRichard  MAGouvernet  J  et al.  The kinetics of the visible growth of a primary melanoma reflects the tumor aggressiveness and is an independent prognostic marker: a prospective study. Int J Cancer 2002;102 (1) 34- 38
PubMed Link to Article
Liu  WDowling  JPMurray  WK  et al.  Rate of growth in melanomas: characteristics and associations of rapidly growing melanomas. Arch Dermatol 2006;142 (12) 1551- 1558
PubMed Link to Article
Herd  RMCooper  EJHunter  JA  et al.  Cutaneous malignant melanoma: publicity, screening clinics and survival: the Edinburgh experience 1982-90. Br J Dermatol 1995;132 (4) 563- 570
PubMed Link to Article
Gerdes  JLemke  HBaisch  H  et al.  Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol 1984;133 (4) 1710- 1715
PubMed
Goto  HTomono  YAjiro  K  et al.  Identification of a novel phosphorylation site on histone H3 coupled with mitotic chromosome condensation. J Biol Chem 1999;274 (36) 25543- 25549
PubMed Link to Article
Liu  WKelly  JWTrivett  M  et al.  Distinct clinical and pathological features are associated with the BRAF(T1799A(V600E)) mutation in primary melanoma. J Invest Dermatol 2007;127 (4) 900- 905
PubMed Link to Article

Figures

Place holder to copy figure label and caption
Figure 1.

Scatterplot of the relationship between the Ki67 score and the clinical rate of growth.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

Scatterplot of the relationship between phosphorylated-histone H3 (PH3) score and the clinical rate of growth.

Graphic Jump Location

Tables

References

Grob  JJRichard  MAGouvernet  J  et al.  The kinetics of the visible growth of a primary melanoma reflects the tumor aggressiveness and is an independent prognostic marker: a prospective study. Int J Cancer 2002;102 (1) 34- 38
PubMed Link to Article
Liu  WDowling  JPMurray  WK  et al.  Rate of growth in melanomas: characteristics and associations of rapidly growing melanomas. Arch Dermatol 2006;142 (12) 1551- 1558
PubMed Link to Article
Herd  RMCooper  EJHunter  JA  et al.  Cutaneous malignant melanoma: publicity, screening clinics and survival: the Edinburgh experience 1982-90. Br J Dermatol 1995;132 (4) 563- 570
PubMed Link to Article
Gerdes  JLemke  HBaisch  H  et al.  Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol 1984;133 (4) 1710- 1715
PubMed
Goto  HTomono  YAjiro  K  et al.  Identification of a novel phosphorylation site on histone H3 coupled with mitotic chromosome condensation. J Biol Chem 1999;274 (36) 25543- 25549
PubMed Link to Article
Liu  WKelly  JWTrivett  M  et al.  Distinct clinical and pathological features are associated with the BRAF(T1799A(V600E)) mutation in primary melanoma. J Invest Dermatol 2007;127 (4) 900- 905
PubMed Link to Article

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