Sabato 27 ottobre 2012 - Pacini Editore

RElaziONi
when Langerhans cells proliferate in bronchiolar wall and
insinuate into the surrounding alveolar septa, forming multiple
stellate nodules centered on small airways. Together with
Langerhans cells, these cellular nodules frequently incorporate
a variable number of eosinophils and smoker’s macrophages,
both in surrounding alveolar spaces and in the interstitium.
An associated RB is almost universal and sometimes
extensive, being visible at CT-scan as ground-glass opacities.
With time, the center of the nodules becomes fibrotic and
irregular cavities develop in some of the nodules, leading to
the classical histological features of mature LCH: multiple
stellate nodules, some of which cavitated and surrounded by
normal lung. The fate of these lesions vary from case to case,
probably depending on the abstinence from smoking and from
individual predisposition. In many cases the nodules reabsorb
completely or leave to small bronchiolocentric scars with
paracicatricial emphysema: it is reasonable to suspect that
some cases of centrilobular emphysema with fibrosis are in
reality examples of healed LCH. In a minority of patients a
progressive fibrosis develops: the stellate shape of the scars,
their bronchiolocentric distribution with a prevalence in the
upper lobes, and the absence/paucity of fibroblastic foci are
characteristic of chronic LCH and are sufficient for a firm
diagnosis in the majority of the cases, even in the absence of
residual Langerhans cells. Occasionally, however, the histo-
Sala Giotto 10.30-12.30
Patologia polmonare 2
La diagnosi molecolare nel carcinoma polmonare
EGFr mutations in nSCLC: methods of detection
and open questions
N. Normanno
Cell Biology and Biotherapy Unit, INT Fondazione “G.Pascale, Naples,
Italy and Pharmacogenomic Laboratory, CROM – Centro Ricerche
Oncologiche di Mercogliano, Mercogliano, Avellino, Italy
Activating mutations of the epidermal growth factor receptor
(EGFR) in non-small-cell lung cancer (NSCLC) have been
discovered following analysis of the EGFR gene in patients
that responded to the EGFR tyrosine kinase inhibitors (TKI)
gefitinib or erlotinib in early clinical trials. Indeed, almost all
patients who respond to EGFR-TKIs have been shown to carry
activating mutations usually found in exons 18 through 21 of
the TK domain of EGFR, and are either point mutations or
in-frame small deletions or insertions. Two mutations, a single
point mutation in exon 21, the L858R, and a series of small inframe
deletions in exon 19, account for approximately 90% of
all EGFR mutations.
EGFR mutations are not frequent in unselected Caucasian
NSCLC patients. However, they are far more frequent in
female patients as compared with male (38.7% versus 10%);
in adenocarcinoma as compared with other histological types
(29.4% versus 1.8%); in non-smokers as compared with current
smokers or former smokers (45.8% versus 7.1%); and in
East-Asian NSCLC patients (33.4%) as compared with Non-
Moderatori: Bruno Murer (Mestre), Luigi Ruco (Roma)
219
logical differential diagnosis with UIP is difficult and requires
a strict correlation with clinical-radiological findings. As for
RB, emphysema and fibrosis, also LCH can be an histological
incidental finding in the lung specimen removed for another
disease, for example carcinoma.
Summary. As we have seen, tobacco smoke can cause in the
lung many histological abnormalities. These abnormalities
can be variably combined one with the others, creating a significant
overlap among the different entities. Moreover, they
frequently provide just a backdrop for other diseases, more
clinically relevant. For these reasons, to establish the significance
of histological findings a close correlation with clinical
and radiological data is mandatory.
Interstiziopatie fumo-correlate
A. Cavazza
Paper not received
La biopsia trans bronchiale: inquadramento
generale e casi paradigmatici
M. Barbareschi
Paper not received
East-Asian patients (5.5%). Results of randomized phase III
clinical trials have clearly demonstrated that administration of
an EGFR TKI results in a prolonged progression free survival
(PFS) as compared with chemotherapy in patients carrying
EGFR mutations. Following these findings, treatment with an
EGFR TKI is the recommended first line therapy for EGFR
mutant patients. As a consequence, assessment of the mutational
status of the EGFR has become mandatory in order to
choose the most appropriate first-line treatment for NSCLC
patients.
Different techniques are currently used for the detection of
EGFR mutations, including PCR/sequencing, pyrosequencing,
Real Time PCR and fragment analysis. Although home
brew methods are widely used for mutational analysis, commercially
available kits have the advantage to provide both
positive and negative controls.
EGFR mutation analysis is not easy. More than 250 mutations
in 4 different exons of the EGFR gene have been described up
to now. Specimens available for EGFR testing are often small
and contain a low percentage of tumor cells. Therefore, low
sensitive techniques might lead to false-negative results. In
contrast, high sensitive methods might lead to false positive
results, if appropriate controls are not used.
Gefitinib was approved in Italy for treatment of NSCLC
patients carrying mutant EGFR in May 2010. Guidelines for
EGFR mutational analysis in NSLC patients were prepared in
2010 by a steering committee of members of the Italian Asso-