**3. Results**

As show the Figure 2, 27.4% of subjects display an AQC with an increased likelihood of malignancy (score equal or higher than 4.6) and 26.1% showed undetermined likelihood of malignancy (score between 3.9 and < 4.6). Among samples with increased AQC (27.4 %), 15.75% and 11.68% were negative and positive (≥ 1 μg/mL) for DR70, respectively. Samples with undetermined AQC showed 22.01% and 4.07% of negative and positive DR70 values, respectively. Among 46.5% of samples that showed decreased likelihood of malignancy, 42.11% were negative and 4.34% were positive for DR70. In the latter group, additional clinical tests confirmed several cancers including colon, breast and one case of prostate cancer, currently under study.

On the other hand, AFB identified PNL (metaplasia and dysplasia) better than the White Light Bronchoscopy (WLB) by itself. As show the Figure 3, AFB detected a zone with a score of 0.67, suspicious of malignance and normal according to WLB. The Histopatholo‐ gy assay informed for the biopsy taking in this zone, increasing in the coarse epithelial and desmosomes and cellular flatting and maturation in the upper layer; in comparison to a normal epithelium (Figure 3B), without cytology atypias; classifying the biopsy as a

Relationship Between Toxicogenomic, Environment and Lung Cancer

http://dx.doi.org/10.5772/55663

67

**Figure 3.** AFB and WLB and Histopathology assay for a Squamous Metaplasia Volunteer A80. Squamous Metaplasia (B) Volunteer A109. Normal Epithelium Stain HE 100x. CeteCáncer. INNOVA CORFO. Thesis Avaria P. MSc, Faculty of

The Figure 4 shows an AFB with a score of 0.83 and suspicious of malignance. The Histopa‐ thology assay informed a considerable cellular increasing in the 2/3 lower, pleomorphism, nuclear heterogeneity, chromatin density increased without mitosis, classifying the biopsy as

Squamous metaplasia (Figure 3A).

Medicine, University of Chile, 2012

mild dysplasia (Figure 4A).

**A B** 

**AFB WLB** 

**Figure 2.** AQC and DR70 correlation and percentage (N) for each LC risk interval. Likehood LC risk: AQC: ≥ 4.6, in‐ creased; ≥ 3.9 ≤ 4.6 undetermined; ≤ 3.9 decreased DR70: ≥ 1.0, increased; ≤ 1.0 decreased

The data shows that DR70 itself might contribute to confirm tumour diagnosis and to identify patients with advanced LC, with high sensitivity (Table 3). However, the test would be better identifying negative LC cases with a high specificity and Negative Predictive Value (NPV). AQC for itself resulted with high sensitivity and specificity for LC with higher NPV than Negative Predictive Value (PPV), confirming especially negative tests, with high precision. Related to PNL, both biomarkers might be used as complemen‐ tary tools to confirm negativity for PNL, showing a higher specificity (98.6%) than both test for itself, keeping a high NPV (97.2%).

On the other hand, AFB identified PNL (metaplasia and dysplasia) better than the White Light Bronchoscopy (WLB) by itself. As show the Figure 3, AFB detected a zone with a score of 0.67, suspicious of malignance and normal according to WLB. The Histopatholo‐ gy assay informed for the biopsy taking in this zone, increasing in the coarse epithelial and desmosomes and cellular flatting and maturation in the upper layer; in comparison to a normal epithelium (Figure 3B), without cytology atypias; classifying the biopsy as a Squamous metaplasia (Figure 3A).

**3. Results**

currently under study.

**13,31 (49)**

66 Oncogenesis, Inflammatory and Parasitic Tropical Diseases of the Lung

**20,38 (75)**

**20,38** 

**38,31 (141)** 

**72 (265)**

test for itself, keeping a high NPV (97.2%).

creased; ≥ 3.9 ≤ 4.6 undetermined; ≤ 3.9 decreased DR70: ≥ 1.0, increased; ≤ 1.0 decreased

**AQC score % (N)**

**27,4 (101)**

**46,5 (171)**

**26,1 (96)**

As show the Figure 2, 27.4% of subjects display an AQC with an increased likelihood of malignancy (score equal or higher than 4.6) and 26.1% showed undetermined likelihood of malignancy (score between 3.9 and < 4.6). Among samples with increased AQC (27.4 %), 15.75% and 11.68% were negative and positive (≥ 1 μg/mL) for DR70, respectively. Samples with undetermined AQC showed 22.01% and 4.07% of negative and positive DR70 values, respectively. Among 46.5% of samples that showed decreased likelihood of malignancy, 42.11% were negative and 4.34% were positive for DR70. In the latter group, additional clinical tests confirmed several cancers including colon, breast and one case of prostate cancer,

0,14 0,88 1,0 5,0 13..

**Figure 2.** AQC and DR70 correlation and percentage (N) for each LC risk interval. Likehood LC risk: AQC: ≥ 4.6, in‐

The data shows that DR70 itself might contribute to confirm tumour diagnosis and to identify patients with advanced LC, with high sensitivity (Table 3). However, the test would be better identifying negative LC cases with a high specificity and Negative Predictive Value (NPV). AQC for itself resulted with high sensitivity and specificity for LC with higher NPV than Negative Predictive Value (PPV), confirming especially negative tests, with high precision. Related to PNL, both biomarkers might be used as complemen‐ tary tools to confirm negativity for PNL, showing a higher specificity (98.6%) than both

**2,44 (9)**

**1,63 (6)**

**3,80 (14)**

**7,9 (29)**

**11,68 (43)**

> **4,07 (15)**

**20,1 (74)**

DR70 µg/mL % (N)

**4,34 (16)**

**Figure 3.** AFB and WLB and Histopathology assay for a Squamous Metaplasia Volunteer A80. Squamous Metaplasia (B) Volunteer A109. Normal Epithelium Stain HE 100x. CeteCáncer. INNOVA CORFO. Thesis Avaria P. MSc, Faculty of Medicine, University of Chile, 2012

The Figure 4 shows an AFB with a score of 0.83 and suspicious of malignance. The Histopa‐ thology assay informed a considerable cellular increasing in the 2/3 lower, pleomorphism, nuclear heterogeneity, chromatin density increased without mitosis, classifying the biopsy as mild dysplasia (Figure 4A).

for itself resulted with high sensitivity and specificity for LC, but showed a higher sensitivity and specificity than DR70 for PNL, 90.9% and 89.4%, respectively. Additionally, both bio‐ markers might be used as complementary tools to confirm negativity for LC and or PNL. In conclusion, as a pre screener for LC, both biomarkers test might be employed with at high specificity/high sensitivity as complementary tools to detect LC. For PNL, both tests would be

Relationship Between Toxicogenomic, Environment and Lung Cancer

http://dx.doi.org/10.5772/55663

69

better confirming negativity than subjecting presence of PNL.

**Figure 5.** Relationship between Autofluorescence Broncoscopy (AFB) and Histopathology Assay (HA)

government programme, that provide additional health services for patients.

This is the first study in Latin America to complement image techniques with cellular and molecular biomarkers, to detect LC and PNL. These results provide scientific and clinical information for Chilean health authorities to include early detection of LC in the AUGE

Our results presented here clearly demonstrate the reliability of both biomarkers to select good candidates for detect LC or pre neoplasic lesions (PNL). These results suggest that both AQC and DR70 might provide transcendentally information not only to confirm or suggest diag‐ nostic for LC, but also to surveillance screening of LC after treatment. It is as important to

**4. Discussion**

**Figure 4.** AFB and WLB and Histopathology assay for a Mild Dysplasia Volunteer A101. Mild Dysplasia (B) Volunteer A109. Normal Epithelium Stain HE 100x. CeteCáncer. INNOVA CORFO. Thesis Avaria P. MSc, Faculty of Medicine, Uni‐ versity of Chile, 2012

Fifty percent of the samples, classified as suspicious (12%) by AFB, were confirmed as metaplasia (33%) or dysplasia (17%) by histopathology. The rest of the samples classified by AFB as suspicious were classified by the histopathology as inflammation (25%) and hyper‐ plasia (25%). Non one was related with a normal histopathology sample (Figure 5).


**Table 1.** Sensitivity and Specificity for DR70 and AQC, for LC and PNL

The data shows that DR70 itself might contribute to confirm tumour diagnosis and to identify patients with advanced LC, with high sensitivity (95.8%) and specificity (91.9%) (Table 1). AQC for itself resulted with high sensitivity and specificity for LC, but showed a higher sensitivity and specificity than DR70 for PNL, 90.9% and 89.4%, respectively. Additionally, both bio‐ markers might be used as complementary tools to confirm negativity for LC and or PNL. In conclusion, as a pre screener for LC, both biomarkers test might be employed with at high specificity/high sensitivity as complementary tools to detect LC. For PNL, both tests would be better confirming negativity than subjecting presence of PNL.

**Figure 5.** Relationship between Autofluorescence Broncoscopy (AFB) and Histopathology Assay (HA)
