Our laboratory performs the whole range of molecular tests required by modern medicine to identify the mutation and thus find the most appropriate treatment for the patient.


A mutation is any change in the sequence of nucleotides in the DNA chain.
Mutations are divided into small-scale and large-scale/recombination mutations.

Small-scale mutations involve one nucleotide (point mutation) or a few nucleotides and include the phenomena of substitution of one nucleotide for another, deletion where one or a few nucleotides are removed from the DNA and insertion where one or a few nucleotides are added to the DNA.

Large-scale mutations involve broad changes in chromosomal structure and include gene amplifications or duplications, chromosomal inversions where a reversal of the orientation of a chromosome segment occurs, chromosomal shuttling where an exchange of genetic material between non-homologous chromosomes occurs, and large-scale deletions or insertions of nucleotides.


DNA methylation is an epigenetic mechanism whereby methyl groups are added to the cytosines in DNA resulting in chromatin compaction and suppression of gene expression. In cancer cells, hypermethylation of promoters of tumour suppressor genes is most commonly observed, resulting in their inactivation.

Gametic and Somatic Mutations

Gametic mutations have the potential to be inherited, as the mutation occurs in either the egg or the sperm cell. 

Somatic mutations are not inherited and are not found in germ cells and arise sporadically in the population.

Molecular pathology recommends the use of molecular techniques and markers to study diseases.
In histopathology, the study of molecular markers complements the information provided by the histological examination and is used to personalise the treatment that will be followed by the patient.

In general, the study of molecular markers serves three purposes, diagnosis, prognosis, and prediction, with several markers, however, overlapping and contributing to more than one category.

1) They refer to indicators that assist in diagnosis

2) Used to provide and obtain additional information that will contribute to a more accurate diagnosis.

3) An increasing number of diagnoses are being exclusively defined by the World Health Organization (WHO) on the basis of their molecular profile.

4) Some markers help to identify underlying familial syndromes.

These markers provide additional information on the aggressiveness of the tumour and thus on the patient's prognosis.

In order to be useful, they must provide additional prognostic information beyond that provided by immunohistochemical staining.

In some cases, the detection of a prognostic factor may influence the oncologist's decision whether to give the patient additional chemotherapy.
For example, in patients with breast cancer, the detection of a high risk of recurrence in Oncotype Dx will usually prompt the oncologist to offer the patient adjuvant chemotherapy.

Predictive markers basically predict which treatments the tumour will respond to.

Markers that predict response to targeted therapy.
By targeting specific molecular changes in tumour cells, these therapies have a strong effect on neoplastic cells without affecting normal cells.
The treatment includes:
1) Tyrosine kinase inhibitors
2) Serine/threonine kinase inhibitors
3) GTPase inhibitors
4) Monoclonal antibodies
5) Inhibitors of DNA repair mechanisms (e.g., PARP inhibitors)

Treatment with these drugs helps to keep the cancer under control and prevent further progression rather than cure it.

However, the cancer gradually develops resistance to treatment (usually 1 to 2 years after initiation):
1) They may develop secondary mutations in the same gene that is targeted
2) May develop other changes in the gene targeted (e.g., amplification)
3) May develop molecular changes in pathways that bypass the targeted gene.

Markers predicting response to immunotherapy

Treatment with immunotherapeutic agents manipulates the immune system to target tumour cells.
Immune checkpoints are molecules expressed by immune cells that moderate the immune response.
Immune checkpoint inhibitors (ICIs) are a type of immunotherapy that blocks the function of immune checkpoints. As a result, tumour cells cannot suppress the immune response against the tumour and the immune system targets the neoplastic cells.
ICIs help to keep the neoplasm under control but increasing reports in the literature also report positive effects in the treatment of metastatic cancer.
Some markers that help predict response to immunotherapy include:
1) PDL-1 expression testing using immunohistochemistry (e.g., non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma, urothelial carcinoma, triple negative breast cancer, esophageal cancer)
2) The control of DNA repair and maintenance mechanism (MMR) protein damage as seen in colorectal cancer, endometrial cancer, upper gastrointestinal cancers and pancreaticobiliary cancers.
3) The measurement of tumor mutation burden (TMB) which refers to the count of the number of mutations carried by cancer cells.

Molecular Testing