Pathological and molecular characteristics distinguishing contralateral metastatic from new primary breast cancer.
BACKGROUND
Breast cancer patients have a cumulative lifetime risk of 2%-15% of developing a contralateral metastatic or ex novo primary cancer. From prognostic and therapeutic viewpoints, it is important to differentiate metastatic from second primary. To distinguish these entities, we investigated whether the pattern of X chromosome inactivation could determine whether the two tumors derived from different progenitor cells.


METHODS
The clonality of bilateral breast cancer was evaluated through the X-inactivation analysis using the human androgen receptor gene (HUMARA) polymorphism and the histopathologic and molecular results were compared. A different or an identical pattern of X inactivation was considered as indicator of a second primary cancer or not informative, respectively. We considered morphological indicators of a new primary cancer the absence of concordance in the histological type or a better histological differentiation.


RESULTS
Ten patients with bilateral breast cancer were evaluated. Morphological criteria indicated that eight were second primary, a conclusion confirmed by the X-inactivation analysis. Two cases classified as recurrence according to morphological criteria were classified as second tumor by molecular analysis.


CONCLUSIONS
Our results show that the HUMARA clonality assay can improve the histological parameters in differentiating metastatic cancer from second primary cancer.
Banelli
B
B
Department of Advanced Diagnostic Technologies, Division of Tumor Genetics.
Casciano
I
I
Department of Advanced Diagnostic Technologies, Division of Tumor Genetics.
Di Vinci
A
A
Department of Advanced Diagnostic Technologies, Division of Tumor Genetics.
Gatteschi
B
B
Department of Advanced Diagnostic Technologies, Division of Pathology.
Levaggi
A
A
Department of Integrated Medical Oncology, Division of Medical Oncology 'A', Istituto Nazionale per la Ricerca sul Cancro, Istituto Scientifico Tumori.
Carli
F
F
Department of Advanced Diagnostic Technologies, Division of Pathology.
Bighin
C
C
Department of Integrated Medical Oncology, Division of Medical Oncology 'A', Istituto Nazionale per la Ricerca sul Cancro, Istituto Scientifico Tumori.
Salvi
S
S
Department of Advanced Diagnostic Technologies, Division of Pathology.
Allemanni
G
G
Department of Advanced Diagnostic Technologies, Division of Tumor Genetics.
Ghiorzo
P
P
Department of Oncology, Biology and Genetics (DOBiG), University of Genova, Genova.
Pronzato
P
P
Department of Integrated Medical Oncology, Division of Medical Oncology 'A', Istituto Nazionale per la Ricerca sul Cancro, Istituto Scientifico Tumori.
Venturini
M
M
Department of Integrated Medical Oncology, Division of Medical Oncology 'A', Istituto Nazionale per la Ricerca sul Cancro, Istituto Scientifico Tumori; Department of Oncology, Sacro Cuore-Don Calabria Hospital, Negrar (Verona), Italy.
Romani
M
M
Department of Advanced Diagnostic Technologies, Division of Tumor Genetics. Electronic address: massimo.romani@istge.it.
Del Mastro
L
L
Department of Integrated Medical Oncology, Division of Medical Oncology 'A', Istituto Nazionale per la Ricerca sul Cancro, Istituto Scientifico Tumori.
D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D002277:Carcinoma / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D002999:Clone Cells / Q000473:pathology; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging / Q000379:methods*; D009378:Neoplasms, Multiple Primary / Q000175:diagnosis / Q000473:pathology; D016133:Polymerase Chain Reaction / Q000379:methods; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis; D054928:Validation Studies as Topic
D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human