Issue 4 - August 2010 - Pacini Editore

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Molecular diagnosis of solid tumours.
A practical approach for organ pathologies
Molecular diagnosis in solid tumor: the breast
A. Sapino, C. Marchiò
Dipartimento di Scienze Biomediche e Oncologia Umana. Torino.
Italy
Molecular techniques are, nowadays, in common use in pathology
laboratories, especially in the field of cancer diagnosis.
In breast pathology, molecular testing continues to expand
as requests by the oncologists of more precise prediction on
response to treatment and risk of recurrence increase.
In situ hybridization techniques, such ad FISH/CISH, SISH
to test HER2 gene status, are the basic and most widely used
molecular tests applied to breast cancer diagnosis. However,
following the results of the first studies of microarrays used
as prognostic/ predictive tools, countless prognostic and/or
predictive signatures have been developed. Two of these
signatures, the MammaPrint ® (Agendia BV, Amsterdam,
Netherlands) and the Oncotype DX ® (Genomic Health Inc.,
Redwood City, CA, USA) have achieved the FDA approval.
In Italy, both of them are commercially available only for
patients’ use. In particular, the first assay is based upon a
multi-gene prognostic predictive score comprising 70 genes
and works on mRNA extracted form fresh cancer tissues.
This signature segregates patients in two categories: one of
good prognosis (“low-risk” group), and one of poor prognosis
(“high-risk” group). The Oncotype DX ® is an RT-PCR based
test that is based on the mRNA expression levels of only 21
genes (16 cancer related genes and 5 reference genes) and is
presented as single Recurrence Score, which is a continuous
variable ranging between 0 and 100 divided into three risk
Moderators: G. Tallini (Bologna), G. Stanta (Trieste)
groups: low (< 18), intermediate (18-31) and high (RS ≥31),
for clinical decision-making. The main goal of both signatures
is to safely spare patients at “low molecular risk” with border
line biological risk from chemotherapy. However extensive
validation of MammaPrint ® and of Oncotype DX ® represents
the main challenge in integrating them in the standard of
breast patients care. Combining molecular assay results with
the pathological and clinical features will pave the way to a
new era in breast oncology.
Molecular diagnosis of lung cancer
A. Marchetti
Sezione di Diagnostica Molecolare, Dipartimento di Oncologia e
Medicina Sperimentale, Università “G. D’Annunzio”, Chieti, Italia
Lung cancer is the most frequent cause of cancer-related
morbidity and mortality in industrialised countries, and about
80% of primary lung cancers are non-small cell lung carcinomas
(NSCLCs). The two most common subtypes of NSCLC,
squamous cell carcinoma (SCC) and adenocarcinoma (AC)
derive from different compartments in the lung. The main
molecular pathways involved in the pathogenesis of NSCLC
include: a) growth promoting pathways (EGFR, KRAS PI3K,
ALK), b) growth inhibitory pathways (p53, Rb, P14ARF,
STK11), c) apoptotic pathways (Bcl-2, Bax, Fas/FasL), d)
pathways involved in DNA repair and immortalisation processes.
A number of epigenetic changes, including DNA
methylation, histone/chromatin protein modification, and
micro-RNA expression can also contribute to tumour develop-