Sabato 27 ottobre 2012 - Pacini Editore

276
role of molecular biology in ovarian cancer
prognostic implications
I. Montagnani, F. Castiglione, A.M. Buccoliero, P. Pretelli,
D. Moncini, D. Rossi Degl’Innocenti, G. Scarselli, G.L. Taddei
Università degli studi di Firenze. AOUC Careggi, Dipartimento di Area
Critica Medico Chirurgica sezione di Anatomia Patologica, Firenze
Epithelial ovarian cancer comprises the majority of the malignant
ovarian tumors in adult woman. These neoplasms are classified
into distinct morphologic categories based on the histologic
appearance into: serous, mucinous, endometrioid, clear cell,
transitional, squamous, mixed and undifferentiated type.This heterogeneous
group of neoplasms is composed of benign tumors in
more than 60% of cases. The malignant form are generally (more
than 90% of cases) detected in advanced stages (III or IV stage)
and in these cases the death for disease arises to 60%. Actually
the first line therapy for these patients is based on traditional chemotherapy
(using cisplatino and taxolo); this treatment influences
the disease-free-survival, but not the mortality.
In this study we select 67 cases of high grade serous ovarian carcinoma
(G3 grade) and we propose to analyse KRAS gene with
PCR Sequencing. We want to identify the presence of mutation
in this gene according to the cancerogenesis progression model
introduced by Robert J. Kurman.
We find that in the case of wild-type KRAS patients have higher
disease-free-survival and that mutated gene (in codon 12 or 13)
occurs precociously in cancerogenesis.
These observations stand out statistic significative prognostic
values of KRAS mutation in high grade serous carcinoma. Furthermore
these results prospect the possibility to use a specific
treatment for these patients using targeted immunotherapy to
increase the overall survival.
Epigenetic alterations in oral cancer:
study of HMLH1, MGMT and rAr-beta-2 by
methylation specific PCr (MSP)
G. Pannone1 , A. Santoro1 , M. Mattoni1 , S. Papagerakis2 ,
S. Staibano3 , G. De Rosa3 , B. Pantaleo1 1 Department of Surgical Sciences, Section of Pathological Anatomy, University
of Foggia, Foggia, Italy; 2 Department of Otolaryngology, Head
and Neck Surgery and Oncology, Medical School University of Michigan
Ann Arbor, Ann Arbor, MI, USA; 3 Department of Biomorphological and
Functional Sciense-Session of Pathological Anatomy- University of Naples
FedericoII, Naples,Italy
Background. Hyper-methylation of cytosine base in CpG islands
of gene promoters is an epigenetic phenomenon able to down
regulate the expression of genes. When an oncogene expression
is influenced, this phenomenon is directly linked with carcinogenesis
1 . In oral district, many genes are considered to cause
OSCC if their methylation status is altered. In our laboratory
we have analysed, in a series of primary OSCCs with matched
normal oral mucosa, the methylation status of a panel of genes,
including hMLH1, MGMT, and RAR-beta-2, in order to define
an epigenetic fingerprint of the oral cancer.
Materials and methods. Thirty-seven cases of formalin-fixed,
paraffin-embedded OSCC with relative controls of normal oral
epithelium were analysed by methylation specific PCR (MSP).
Also in this work we have observed different frequencies of gene
methylation. For all genes, the Wald Test and the logistic multiple
regression were performed, in order to verify the association
between methylation status of gene promoter (covariates) and
presence of cancer (response variable).
Results. Characteristically, and in addition to the literature
reported data, we have noted that also the healthy oral mucosa
shows a methylated background. In our study population the
most frequently methylated gene in cancer was represented by
hMLH1(53%), although higher levels of methylation were found
CONGRESSO aNNualE di aNatOmia patOlOGiCa SiapEC – iap • fiRENzE, 25-27 OttOBRE 2012
in control oral mucosa. RAR-beta-2 and MGMT promoter hypermethylation
was found in both cases only in 13.5% of OSCCs,
but more frequently in healthy oral mucosa (respectively, 28.5%
and 23% of studied cases). Therefore, The Wald test confirmed
the statistical significance for RAR-beta-2 (p = 0.044; CI at 95%).
Conclusions. Similarly to other reviewed and here commented
works, this study highlights the importance of epigenetic silencing,
showing that a panel of genes may be useful in clinical
practice separating normal oral epithelia from the cancerous
ones if their DNAs were analysed by methylation specific PCR
technique. All these results not only shed light on a molecular
mechanism contributing to OSCC tumorigenesis, but also suggest
that employing of an epigenetic fingerprint, together with the
classical histo-pathological parameters, may improve the current
diagnostic tools, but also contribute indirectly to therapeutics as
predictor of choice for the correct clinical management of oral
neoplastic and pre-neoplastic lesions.
references
1 Kulkarni V, Saranath D. Concurrent hypermethylation of multiple
regulatory genes in chewing tobacco associated oral squamous cell
carcinomas and adjacent normal tissues. Oral Oncol 2004;40:145-53.
2 Pannone G, Bufo P, Santoro A, et al. WNT pathway in oral cancer:
epigenetic inactivation of WNT-inhibitors. Oncol Rep 2010;24:1035-41.
The endometriotic ovarian cysts:
diagnostic possibility in molecular biology
P. Pretelli, F. Castiglione, D. Moncini, A.M. Buccoliero, E. Projetto,
I. Montagnani, D. Rossi Degl’Innocenti, G.L. Taddei
Università di Firenze Dipartimento di Area Critica Medico- Chirurgica.
Sezione di Anatomia Patologica
Endometriosis is one of the most common benign disorders which
affects 10-15% of all women in reproductive age. This pathology
is defined as the presence of endometrial-like tissue (glands
and stroma) outside the uterine cavity. The ectopic endometrium
responds, as the normal endometrium, to stimuli of the ovarian hormones,
especially estrogen, taking attitudes proliferative and functional
typical of the normal endometrium. This induces a chronic
inflammatory reaction, scar tissue, and adhesions that may distort a
woman’s pelvic anatomy. Endometriosis is a debilitating condition
characterized by high recurrence rates. Patients with endometriosis
mainly complain of pelvic pain, dysmenorrhea, and dyspareunia.
The etiology and pathogenesis remain unclear.
Homeobox genes are regulatory genes with a common 180-183
bp sequenze (homeobox) coding for a 61 amino-acis domain
definite as homeodomain. This homeodomain is a DNA binding
domain and acts as transcription factor during normal embryonic
development. In human class homeobox genes, also termed HOX
genes, are organized in 4 cluster HOXA, HOB, HOXC and HOXD,
situated on separated chromosomes, 7, 12, 17 and 2, respectively.
Each cluster contain between 9-11 genes for a total of 39 clustered
human Hox genes. During development, Hox genes are expressed
in accordance with gene position within its cluster and in rostralcaudal
manner. In the last years was born a interest on a possible
role of human Hox genes and many studies are trying to find a relation
between an inappropriate expression of these genes and tumor
progression and metastasis, nevertheless HOX genes are also expressed
in normal cells to maintain the tissue and organ physiology.
The differential diagnosis of endometriotic lesion compared to
non endometriotic lesion is important for the management of
these patients to establish an adequate pharmacologic therapy.
The diagnosi of endometriotic disease may be clinically suspected
by the patient’s history and by the surgeon’s evaluation,
but it can only be established by histopathological evaluation.
Sometimes the histological diagnosis of endometriosis is very
difficult because of the changes occurring in the lesions after
bleeding and fibrosis.